Spatially resolved reflectance from turbid media having a rough surface. Part II: experiments.

Spatially resolved reflectance measurements are a standard tool for determining the absorption and scattering properties of turbid media such as biological tissue. However, in literature, it was shown that these measurements are subject to errors when a possible rough surface between the turbid medium and the surrounding is not accounted for. We evaluated these errors by comparing the spatially resolved reflectance measured on rough epoxy-based samples with Monte Carlo simulations using Lambertian surface scattering, the Cook-Torrance model, and the generalized Harvey-Shack model as surface scattering models. To this aim, goniometric measurements on the epoxy-based samples were compared to the angularly resolved reflectance of the three surface models to estimate the corresponding model parameters. Finally, the optical properties of the phantoms were determined using a Monte Carlo model with a smooth surface.

Influence of Lambertian surface scattering on the spatially resolved reflectance from turbid media: a computational study.

The determination of the optical properties in turbid media plays an essential role in medical diagnostics and process control. The method of spatially resolved reflectance measurements is a frequently used tool to evaluate the reduced scattering coefficient as well as the absorption coefficient. In most cases a smooth interface is assumed between the medium under investigation and the surrounding medium. However, in reality, a rough surface is present at the interface, which alters the light interaction with the surface and volume of the turbid medium. Hence, the idea behind this paper was to investigate the influence of rough surfaces on the spatially resolved reflectance and thus on the determination of the optical properties of turbid media. Particularly, the influence of a Lambertian scattering surface on the result of Monte Carlo simulations of a spatially resolved reflectance setup is shown. In addition, we distinguish between the different interaction modes of surface scattering on the spatially resolved reflectance. There is a strong influence of roughness when the light enters and leaves the turbid medium. Furthermore, the simulations show that, especially for small reduced scattering coefficients and absorption coefficients, large errors in the determination of the optical properties are obtained.

A Critical Review on the Standardization and Quality Assessment of Nonfunctional Laboratory Tests Frequently Used to Identify Inborn Errors of Immunity.

Inborn errors of immunity (IEI), which were previously termed primary immunodeficiency diseases, represent a large and growing heterogeneous group of diseases that are mostly monogenic. In addition to increased susceptibility to infections, other clinical phenotypes have recently been associated with IEI, such as autoimmune disorders, severe allergies, autoinflammatory disorders, benign lymphoproliferative diseases, and malignant manifestations. The IUIS 2019 classification comprises 430 distinct defects that, although rare individually, represent a group affecting a significant number of patients, with an overall prevalence of 1:1,200-2,000 in the general population. Early IEI diagnosis is critical for appropriate therapy and genetic counseling, however, this process is deeply dependent on accurate laboratory tests. Despite the striking importance of laboratory data for clinical immunologists, several IEI-relevant immunoassays still lack standardization, including standardized protocols, reference materials, and external quality assessment programs. Moreover, well-established reference values mostly remain to be determined, especially for early ages, when the most severe conditions manifest and diagnosis is critical for patient survival. In this article, we intend to approach the issue of standardization and quality control of the nonfunctional diagnostic tests used for IEI, focusing on those frequently utilized in clinical practice. Herein, we will focus on discussing the issues of nonfunctional immunoassays (flow cytometry, enzyme-linked immunosorbent assays, and turbidimetry/nephelometry, among others), as defined by the pure quantification of proteins or cell subsets without cell activation or cell culture-based methods.

Assessment of Cardiovascular Risk in Women with Periodontal Diseases According to C-reactive Protein Levels.

Cardiovascular diseases (CVD) are highly prevalent non-communicable diseases worldwide. Periodontitis may act as a non-traditional cardiovascular risk (CVR) factor, linked by a low-grade systemic inflammation mediated by C-reactive protein (CRP). Patients with periodontitis reported higher serum CRP levels; however, a CRP systemic and periodontal correlation in gingival crevicular fluid (GCF) and its CVR impact have been barely studied. We aimed to assess the association between periodontal diseases and CVR in a group of adult women, based on serum high-sensitivity CRP (hs-CRP) levels; and secondly, to determine the association between serum and GCF CRP levels. Gingival crevicular fluid and blood samples were obtained from women with periodontitis, gingivitis, and healthy controls. Serum and GCF CRP were determined by turbidimetric method and Luminex technology, respectively. Data were analyzed and adjusted by CVR factors. All women presented moderate CVR, without an evident association between serum hs-CRP levels and periodontal diseases. While serum hs-CRP concentrations did not significantly differ between groups, patients with gingivitis and periodontitis showed higher CRP levels in GCF, which positively correlated to CRP detection in serum.

A comparison between plausible models in layered turbid media with geometrical variations applying a Bayesian selection criterion.

One possible application of Near Infrared techniques is to analyze human brain metabolic activity. Currently used models take into account the layered structure of the human head but, usually, they do not consider the non-planar surface of some of the boundaries, i.e. gray matter, which results in a much more complex structure, thus leading to more sophisticated models and longer calculation times. The main objective of this work is to determine if it is worth to replace a planar layered structure by a non-planar one. To this end we implement a Bayesian-based quantitative methodology for choosing between two competitive models describing light propagation in layered turbid media. Experiments of time-resolved diffuse reflectance measurements are performed in layered phantoms and complemented with numerical calculations. The resulting Distributions of Time of Flight of both models are compared using Bayesian model selection analysis. The non-planar interface was introduced in the simulations by a simple surface parametrization. Results suggest that, under certain conditions, a multilayer model with planar boundaries is good enough.

Analysis of estimation of optical properties of sub superficial structures in multi layered tissue model using distribution function method.

BACKGROUND AND OBJECTIVE: This paper is focused on the analysis of a method of estimation of the absorption and scattering coefficients of nonhomogeneous two layered structures in time resolved near infrared spectroscopy using method based on cumulative distributions of time of flight of photons. METHODS: The research is based on the analysis of the superposition of cumulative distributions of time of flight of photons. This approach allows for detailed analysis of small variations in characteristics of time of flight of photons caused by an electromagnetic propagation in highly scattering non-homogeneous media. The method presented, based on the variation of statistical minimum distance estimation, is compared to the method of standard curve fitting. It is analyzed by fitting the results obtained from Monte-Carlo simulations of light propagation in the turbid medium to the data from the simulated measurements. RESULTS: The analysis is carried out for a vast range of optical properties of two layered medium in reflectance geometry. CONCLUSIONS: The method allows the estimation of the optical parameters despite the noise in the measured signal, with higher accuracy and generally with smaller number of error function evaluations.

A Low-Cost Micro-Volume Nephelometric System for Quantitative Immunoagglutination Assays.

Immunoassays have been widely used in scientific research and clinical diagnosis due to their versatile detection capability and high specificity. Immunoagglutination assays are kinds of immunoassay, which can simply and rapidly measure the concentration of analytes. In this work, we developed a low-cost micro-volume nephelometric system for quantitative immunoagglutination assays. We used off-the-shelf components to build the system, and the total cost of key components is only about 20 US dollars. The total detection volume in our system was as low as 3 µL, which could significantly reduce the reagent cost and required sample volume. We further evaluated the system performance via the immunoagglutination assay to measure the concentration of C-reactive protein, a plasma protein with levels rising in response to inflammation. The results demonstrated that our system could measure the concentration of analytes with relatively high sensitivity and precision within four minutes, and has high potential to be applied for clinical diagnostic tests.

Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro.

Lactoferrin (LF) and osteopontin (OPN) are both multi-functional whey proteins present at high levels in human milk. These two proteins have a high affinity for each other due to their opposite charges; LF is a basic glycoprotein while OPN is an acidic phosphorylated glycoprotein. LF and OPN were identified to bind to each other over a decade ago, but potential functions of their complex remain unexplored. In this work, we investigated the characteristics of the LF-OPN complex with a focus on its bioactivities. Our results reveal a stronger stability of the LF-OPN complex towards in vitro digestion and more effective binding and uptake by human intestinal cells (HIEC) than LF or OPN alone show. Moreover, the LF-OPN complex promotes proliferation and differentiation of intestinal cells significantly more than the individual proteins do and shows an effect on anti-bacterial function and immune-stimulatory activities intermediate between those of LF and OPN. Thus, by forming a complex in human milk, LF and OPN may protect each other against proteolysis and enhance their individual bioactivities.

[Determination of the immunoglobulin G supply in the newborn calf]. / Bestimmung der Immunglobulin-G-Versorgung beim neugeborenen Kalb.

A sufficient supply of colostral antibodies within the first hours of life is crucial for the development and the health status in young calves. It is rational to examine the immunoglobulin uptake of single animals, but particularly on a herd basis, during herd controls and consultations. This enables economical calf rearing in accordance with animal welfare. Because of the costly, laboratory-dependent and in part time-consuming direct measurement of the absorbed immunoglobulins using radial immunodiffusion (RID) or ELISA, multiple studies attempted to develop indirect methods, which would be affordable and operational in the field. These aim to draw an inference for the absorbed quantity of colostral antibodies based on other correlated parameters. Multiple validations showed in part significant differences between various methods concerning specificity and sensitivity in comparison to the direct methods. In addition to RID and ELISA, this article presents the measurement of the γ-glutamyltransferase (GGT) activity, the determination of the total serum protein concentration using refractometry and the zinc sulphate turbidity test, and describes the advantages and disadvantages of their application. Refractory measurement and determination of the GGT activity represent a valuable alternative to a laboratory-dependent immunoglobulin G measurement. Nevertheless, there is no ideal rapid test method, such that several influencing factors have to be considered.

Quantitative measurement of urinary proteins in 2018: advantages, disadvantages, limits.

Today, there is no reference method for the measurement of urinary proteins. The difficulties are that urine is a very complex biological fluid, and that there are a high intra-and inter-individual variability in the protein excretion rate. Progress has been made during the last thirty years, but high analytical variability persists among the colorimetric or turbidimetric methods used for urinary proteins measurement.

Study on the influence of optical absorption on polarization characterization of tissues.

Absorption effect is a basic optical phenomenon and an important feature in tissue imaging and characterization. Based on our Monte Carlo simulation on the anisotropic tissue model (sphere-cylinder birefringence model), combined with our experiments of tissue phantoms, we demonstrate the influence of absorption effect on Mueller matrix and particularly on depolarization, linear retardance, and diattenuation parameters. The simulation and experimental results show a good consistency on the suppressed depolarization and scatterering induced retardance, and the enhanced diattenuation caused by the absorption, and also indicate the birefringence induced retardance insensitive to the absorption. Study of the phase function of different incident polarized lights and the distribution of scattering number gives a preliminary explanation about the above results.

Assessment of the Multi-Objective Reservoir Operation for Maintaining the Turbidity Maximum Zone in the Yangtze River Estuary.

The construction of multifunction reservoirs is important for flood control, agriculture irrigation, navigation, and hydropower generation, but dam construction will inevitably affect the downstream flow and sediment regimes, which can cause some environmental and ecological consequences. Therefore, this paper aims to propose a framework for assessing the multiobjective reservoir operation model based on environmental flows for sustaining the suspended sediment concentration (SSC) requirements in the turbidity maximum zone (TMZ). The Yangtze River Estuary was used as a case study. Through using an analytical model, a quantitative correlation between SSC and water flow rate was established. Then, the quantitative correlation and the SSC requirements were applied to determine the environmental flows for the estuarine TMZ. Subsequently, a multiobjective reservoir operation model was developed for the Three Gorges Reservoir (TGR), and an improved nondominated sorting genetic algorithm III based on elimination operator was applied to the model. An uncertainty analysis and a comparative analysis were used to assess the model's performance. The results showed that the proposed multiobjective reservoir operation model can reduce ecological deficiency under wet, normal, and dry years by 33.65%, 35.95%, and 20.98%, with the corresponding hydropower generation output lost by 3.37%, 3.88%, and 2.95%, respectively. Finally, we discussed ecological satiety rates under optimized and practical operation of the TGR in wet, normal, and dry years. It indicated that the multiobjective-optimized runoff performs better at maintaining the TMZ in the Yangtze River Estuary than practical runoff. More importantly, the results can offer guidance for the management of the TGR to improve the comprehensive development and protection of the estuarine ecological environment.

Serum Beta-Trace Protein for Assessment of Kidney Function in Neonates.

INTRODUCTION: Compared to the conventional methods, serum beta-trace protein (BTP) has been shown to be more helpful for estimating glomerular filtration rate; however, its value is remained unclear in neonates. The present study aimed to investigate the range of serum BTP level in healthy term neonates and its value to estimate glomerular filtration rate. MATERIALS AND METHODS: This cross-sectional study was conducted on 50 healthy term neonates without underlying cardiovascular or kidney disorders who were admitted to Ali Asghar hospital in 2013. Serum BTP was measured using an automated nephelometric immunoassay. Glomerular filtration rate was assessed using the Schwartz equation based on serum creatinine level. RESULTS: The mean age of the neonates was 6.2 ± 3.6 days (range, 2 to 17 days), their mean gestational age was 38.02 ± 0.20 weeks, and their mean height was 49.8 ± 1.7 cm. The mean serum BTP level was 0.41 ± 0.11 mg/L (range, 0.19 mg/L to 0.92 mg/L). The mean serum creatinine level was 0.49 ± 0.16 mg/dL (range, 0.3 mg/dL to 1.0 mg/dL). The mean estimated GFR was 48.90 ± 15.88 mL/min. A positive correlation was observed between the reciprocal concentrations of BTP and GFR (r = 0.383, P = .006). Furthermore, the reciprocal concentrations of BTP was associated with the reciprocal concentrations of serum creatinine level (r = 0.365, P = .009). CONCLUSIONS: Measurement of serum BTP can be a reliable tool for detecting kidney function in neonates. Further studies are warranted to design a suitable formula for GFR estimation based on serum BTP in neonates.

Performance assessment of a portable nephelometer for outdoor particle mass measurement.

The availability of portable nephelometers has improved assessment of exposure to atmospheric particles at a high resolution regarding space and time. However, nephelometer performance has seldom been evaluated for outdoor measurements, especially in Chinese cities. During 37 days of measurements at four outdoor sites in Shanghai, we assessed a popular nephelometer called SidePak (TSI Inc., USA) for PM1.0, PM2.5 and PM10 mass measurements and compared them to US federal reference methods (FRMs) based on different measurement principles. The nephelometer showed high measurement precision and stability and was strongly correlated with FRMs, making it superior to the portable light scattering monitors reported in the past and thus indicating the maturity of this principle. The nephelometer measurements overestimated all those of FRMs by a factor of two, which is higher than in evaluations in other international cities. This overestimation showed a descending order for PM1.0 (2.9-fold), PM2.5 (2.2-fold) and PM10 (1.9-fold) relative to the FRMs of tapered element oscillating microbalance or beta attenuation combined with nephelometry, based on whole samples. Sites that are far from direct pollution sources showed very good agreement between the nephelometer and FRMs for PM2.5 mass measurements, while, by comparison, the roadside site showed a lower SidePak/FRM PM2.5 ratio, which is likely due to higher abundance of elemental carbon in roadside particles. Relative humidity (RH) was shown to be a key factor that distorted the measurement of the nephelometer. An empirical formula incorporating an RH adjustment developed to correct the nephelometer could produce a reasonable result, even across the various sites. This study demonstrates the great potential of the nephelometer for outdoor particle mass measurements, but for accurate and comparable data, a site-specific calibration is strongly recommended before using.

Massively parallel simulator of optical coherence tomography of inhomogeneous turbid media.

BACKGROUND AND OBJECTIVE: An accurate and practical simulator for Optical Coherence Tomography (OCT) could be an important tool to study the underlying physical phenomena in OCT such as multiple light scattering. Recently, many researchers have investigated simulation of OCT of turbid media, e.g., tissue, using Monte Carlo methods. The main drawback of these earlier simulators is the long computational time required to produce accurate results. We developed a massively parallel simulator of OCT of inhomogeneous turbid media that obtains both Class I diffusive reflectivity, due to ballistic and quasi-ballistic scattered photons, and Class II diffusive reflectivity due to multiply scattered photons. METHODS: This Monte Carlo-based simulator is implemented on graphic processing units (GPUs), using the Compute Unified Device Architecture (CUDA) platform and programming model, to exploit the parallel nature of propagation of photons in tissue. It models an arbitrary shaped sample medium as a tetrahedron-based mesh and uses an advanced importance sampling scheme. RESULTS: This new simulator speeds up simulations of OCT of inhomogeneous turbid media by about two orders of magnitude. To demonstrate this result, we have compared the computation times of our new parallel simulator and its serial counterpart using two samples of inhomogeneous turbid media. We have shown that our parallel implementation reduced simulation time of OCT of the first sample medium from 407 min to 92 min by using a single GPU card, to 12 min by using 8 GPU cards and to 7 min by using 16 GPU cards. For the second sample medium, the OCT simulation time was reduced from 209 h to 35.6 h by using a single GPU card, and to 4.65 h by using 8 GPU cards, and to only 2 h by using 16 GPU cards. Therefore our new parallel simulator is considerably more practical to use than its central processing unit (CPU)-based counterpart. CONCLUSIONS: Our new parallel OCT simulator could be a practical tool to study the different physical phenomena underlying OCT, or to design OCT systems with improved performance.

Combined use of Kappa Free Light Chain Index and Isoelectrofocusing of Cerebro-Spinal Fluid in Diagnosing Multiple Sclerosis: Performances and Costs.

BACKGROUND: Isoelectrofocusing (IEF) to detect oligoclonal bands (OBCs) in cerebrospinal fluid (CSF) is the gold standard approach for evaluating intrathecal immunoglobulin synthesis in multiple sclerosis (MS) but the kappa free light chain index (KFLCi) is emerging as an alternative marker, and the combined/sequential uses of IEF and KFLCi have never been challenged. METHODS: CSF and serum albumin, IgG, kFLC and lFLC were measured by nephelometry; albumin, IgG and kFLC quotients as well as Link and kFLC indexes were calculated; OCBs were evaluated by immunofixation. A total of 150 consecutive patients: 48 with MS, 32 with other neurological inflammatory diseases (NID), 62 with neurological non-inflammatory diseases (NNID), and 8 without any detectable neurological disease (NND) were investigated. RESULTS: Both IEF and KFLCi showed a similar accuracy as diagnostic tests for multiple sclerosis. The high sensitivity and specificity associated with the lower cost of KFLCi suggested to use this test first, followed by IEF as a confirmative procedure. The sequential use of IEF and KFLCi showed high diagnostic efficiency with cost reduction of 43 and 21%, if compared to the contemporary use of both tests, or the unique use of IEF in all patients. CONCLUSIONS: The "sequential testing" using KFLCi followed by IEF in MS represents an optimal procedure with accurate performance and lower costs.

Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays.

BACKGROUND: The measurement of circulating free light chain (FLC) is essential in the diagnosis, prognostic stratification and evaluation of response to therapy in light chain (AL) amyloidosis. For more than 10 years, this has been done with an immunonephelometric assay based on polyclonal antibodies (Freelite), and cutoffs for staging and response assessment have been validated with this method. Recently, a new assay based on monoclonal antibodies (N latex FLC) has been marketed in Europe. METHODS: We evaluated and compared the clinical performance of the two assays in 426 patients with newly diagnosed AL amyloidosis. RESULTS: We found suboptimal agreement between the two methods, with differences between values obtained with the Freelite and N latex FLC assays increasing with the concentration of clonal FLC. The diagnostic sensitivity of the Freelite (82%) and N latex FLC (84%) assays was similar, and both improved to 98% in combination with serum and urine immunofixation. The concentration of FLC measured with both methods had prognostic significance. Less pronounced decreases in FLC best predicted improved survival with the N latex FLC assay (33% vs. 50%), and there was poor concordance (84%) in discrimination of responders. CONCLUSIONS: The two assays have similar diagnostic and prognostic performance. However, they are not interchangeable, and follow-up should be done with either one. New response criteria are needed for the N latex FLC assay.

High-throughput and automated diagnosis of antimicrobial resistance using a cost-effective cellphone-based micro-plate reader.

Routine antimicrobial susceptibility testing (AST) can prevent deaths due to bacteria and reduce the spread of multi-drug-resistance, but cannot be regularly performed in resource-limited-settings due to technological challenges, high-costs, and lack of trained professionals. We demonstrate an automated and cost-effective cellphone-based 96-well microtiter-plate (MTP) reader, capable of performing AST without the need for trained diagnosticians. Our system includes a 3D-printed smartphone attachment that holds and illuminates the MTP using a light-emitting-diode array. An inexpensive optical fiber-array enables the capture of the transmitted light of each well through the smartphone camera. A custom-designed application sends the captured image to a server to automatically determine well-turbidity, with results returned to the smartphone in ~1 minute. We tested this mobile-reader using MTPs prepared with 17 antibiotics targeting Gram-negative bacteria on clinical isolates of Klebsiella pneumoniae, containing highly-resistant antimicrobial profiles. Using 78 patient isolate test-plates, we demonstrated that our mobile-reader meets the FDA-defined AST criteria, with a well-turbidity detection accuracy of 98.21%, minimum-inhibitory-concentration accuracy of 95.12%, and a drug-susceptibility interpretation accuracy of 99.23%, with no very major errors. This mobile-reader could eliminate the need for trained diagnosticians to perform AST, reduce the cost-barrier for routine testing, and assist in spatio-temporal tracking of bacterial resistance.