Forehead monitoring of heart rate in neonatal intensive care.

Heart rate is an extremely important physiological parameter to measure in critically unwell infants, as it is the main physiological marker that changes in response to a change in infant condition. Heart rate is routinely measured peripherally on a limb with a pulse oximeter. However, when infants are critically unwell, the blood supply to these peripheries is reduced in preference for central perfusion of vital organs such as the brain and heart. Measurement of heart rate with a reflection mode photoplethysmogram (PPG) sensor on the forehead could help minimise this problem and make it easier for other important medical equipment, such as cannulas, to be placed on the limbs. This study compares heart rates measured with a forehead-based PPG sensor against a wrist-based PPG sensor in 19 critically unwell infants in neonatal intensive care collecting 198 h of data. The two heart rates were compared using positive percentage agreement, Spearman's correlation coefficient and Bland-Altman analysis. The forehead PPG sensor showed good agreement with the wrist-based PPG sensor with limits of agreement of 8.44 bpm, bias of -0.22 bpm; positive percentage agreement of 98.87%; and Spearman's correlation coefficient of 0.9816. The analysis demonstrates that the forehead is a reliable alternative location for measuring vital signs using the PPG.

Optical fiber sensors for monitoring in critical care.

Monitoring of key physiological and pharmacological parameters is an important part of a closed loop control system in critical care. Optical fiber sensors provide a versatile platform technology that can be easily incorporated into existing in-dwelling catheters or face masks. With appropriate functional coatings they can be used to monitor a range of relevant parameters and two different examples are presented: (i) respiration monitoring; (ii) drug level monitoring. Respiration monitoring involves monitoring of temperature and humidity in inhaled and exhaled breath. The optical fiber sensor consists of a fiber Bragg grating to measure temperature and a tip coating whose refractive index changes with humidity. The sensor is demonstrated to be able to track breath to breath changes when incorporated into a mask. Drug level monitoring is demonstrated in vitro using a long period grating coated with molecularly imprinted polymer nanoparticles that are sensitive to fentanyl. The sensor has a limit of detection of 50ng/ml.

Scaling of the surface vasculature on the human placenta.

The networks of veins and arteries on the chorionic plate of the human placenta are analyzed in terms of Voronoi cells derived from these networks. Two groups of placentas from the United States are studied: a population cohort with no prescreening, and a cohort from newborns with an elevated risk of developing autistic spectrum disorder. Scaled distributions of the Voronoi cell areas in the two cohorts collapse onto a single distribution, indicating common mechanisms for the formation of the complete vasculatures, but which have different levels of activity in the two cohorts.

Highly sensitive optical fibre long period grating biosensor anchored with silica core gold shell nanoparticles.

An optical fibre long period grating (LPG), modified with a coating of silica core gold shell (SiO2:Au) nanoparticles (NPs) deposited using the layer-by-layer method, was employed for the development of a biosensor. The SiO2:Au NPs were electrostatically assembled onto the LPG with the aid of a poly(allylamine hydrochloride) (PAH) polycation layer. The LPG sensor operates at the phase matching turning point to provide the highest sensitivity. The SiO2:Au NPs were modified with biotin, which was used as a ligand for streptavidin (SV) detection. The sensing mechanism is based on the measurement of the refractive index change induced by the binding of the SV to the biotin. The effect on sensitivity of increasing the surface area by virtue of the SiO2:Au nanoparticles' diameter and film thickness was studied. The lowest measured concentration of SV was 2.5nM, achieved using an LPG modified with a 3 layer (PAH/SiO2:Au) thin film composed of SiO2 NPs of 300nm diameter with a binding constant of k=1.7(pM)(-1), sensitivity of 6.9nm/ng/mm(2) and limit of detection of 19pg/mm(2).

Post-processing of polymer foam tissue scaffolds with high power ultrasound: a route to increased pore interconnectivity, pore size and fluid transport.

The aim of this work is to demonstrate that the structural and fluidic properties of polymer foam tissue scaffolds, post-fabrication but prior to the introduction of cells, can be engineered via exposure to high power ultrasound. Our analysis is supported by measurements of fluid uptake during insonification and imaging of the scaffold microstructure via X-ray computed tomography, scanning electron microscopy and acoustic microscopy. The ultrasonic treatment is performed with a frequency of 30 kHz, average intensities up to 80,000 Wm(-2) and exposure times up to 20 h. The treatment is found to increase the mean pore size by over 10%. More striking is the improvement in fluid uptake: for scaffolds with only 40% water uptake via standard immersion techniques, we can routinely achieve full saturation of the scaffold over approximately one hour of exposure. These desirable modifications occur with negligible loss of scaffold integrity and mass, and are optimized when the ultrasound treatment is coupled to a pre-wetting stage with ethanol. Our findings suggest that high power ultrasound is highly targeted towards flow obstructions in the scaffold architecture, thereby providing an efficient means to promote pore interconnectivity and fluid transport in thick foam tissue scaffolds.

Pulsed ultrasound modulated optical tomography utilizing the harmonic response of lock-in detection.

Ultrasound modulated optical tomography (USMOT) can image the optical properties of a scattering medium at a spatial resolution approaching that of ultrasound (US). A lock-in parallel speckle detection technique is proposed to detect pulsed US modulated light using a multipixel detector. The frequency components of the pass band match those of the US pulse train and provide efficient detection. The modulation depth is extracted by taking the difference between a pair of speckle patterns modulated by a pair of phase-inversed US bursts. Modification to pulse inversion mode enables the second harmonic US modulation due to nonlinear US propagation to be detected.

64×64 pixel smart sensor array for laser Doppler blood flow imaging.

What is believed to be the first fully integrated two-dimensional complementary metal oxide semiconductor (CMOS) imaging array for laser Doppler blood flow imaging is demonstrated. The sensor has 64×64 pixels and includes both analog and digital on-chip processing electronics. This offers several potential advantages over commercial sensors as the processing is tailored to the signals of interest and the data bottleneck that exists between the sensor and processing electronics is overcome. To obtain a space efficient design over 64×64 pixels means that standard processing electronics used off-chip cannot be implemented. Images of both simulated blood flow responses and a blood flow occlusion test demonstrate the capability.

Longitudinal acoustic properties of poly(lactic acid) and poly(lactic-co-glycolic acid).

Acoustics offers rich possibilities for characterizing and monitoring the biopolymer structures being employed in the field of biomedical engineering. Here we explore the rudimentary acoustic properties of two common biodegradable polymers: poly(lactic acid) and poly(lactic-co-glycolic acid). A pulse-echo technique is developed to reveal the bulk speed of sound, acoustic impedance and acoustic attenuation of small samples of the polymer across a pertinent temperature range of 0-70 °C. The glass transition appears markedly as both a discontinuity in the first derivative of the speed of sound and a sharp increase in the acoustic attenuation. We further extend our analysis to consider the role of ethanol, whose presence is observed to dramatically modify the acoustic properties and reduce the glass transition temperature of the polymers. Our results highlight the sensitivity of acoustic properties to a range of bulk properties, including visco-elasticity, molecular weight, co-polymer ratio, crystallinity and the presence of plasticizers.

A field-programmable gate array based system for high frame rate laser Doppler blood flow imaging.

This paper presents a general embedded processing system implemented in a field-programmable gate array providing high frame rate and high accuracy for a laser Doppler blood flow imaging system. The proposed system can achieve a basic frame rate of flow images at 1 frame/second for 256 x 256 images with 1024 fast Fourier transform (FFT) points used in the processing algorithm. Mixed fixed-floating point calculations are utilized to achieve high accuracy but with a reasonable resource usage. The implementation has a root mean square deviation of the relative difference in flow values below 0.1% when compared with a double-precision floating point implementation. The system can contain from one or more processing units to obtain the required frame rate and accuracy. The performance of the system is significantly higher than other methods reported to date. Furthermore, a dedicated field-programmable gate array (FPGA) board has been designed to test the proposed processing system. The board is linked with a laser line scanning system, which uses a 64 x 1 photodetector array. Test results with various operating parameters show that the performance of the new system is better, in terms of noise and imaging speed, than has been previously achieved.

Tracking large solid constructs suspended in a rotating bioreactor: A combined experimental and theoretical study.

We present a combined experimental and theoretical study of the trajectory of a large solid cylindrical disc suspended within a fluid-filled rotating cylindrical vessel. The experimental set-up is relevant to tissue-engineering applications where a disc-shaped porous scaffold is seeded with cells to be cultured, placed within a bioreactor filled with nutrient-rich culture medium, which is then rotated in a vertical plane to keep the growing tissue construct suspended in a state of "free fall." The experimental results are compared with theoretical predictions based on the model of Cummings and Waters (2007), who showed that the suspended disc executes a periodic motion. For anticlockwise vessel rotation three regimes were identified: (i) disc remains suspended at a fixed position on the right-hand side of the bioreactor; (ii) disc executes a periodic oscillatory motion on the right-hand side of the bioreactor; and (iii) disc orbits the bioreactor. All three regimes are captured experimentally, and good agreement between theory and experiment is obtained. For the tissue engineering application, computation of the fluid dynamics allows the nutrient concentration field surrounding a tissue construct (a property that cannot be measured experimentally) to be determined (Cummings and Waters, 2007). The implications for experimental cell-culture protocols are discussed.

In situ monitoring of 3D in vitro cell aggregation using an optical imaging system.

Bioreactor systems that maintain cells and tissues in suspension are increasingly popular for culturing 3D constructs to avoid the loss of in vivo cell function associated with traditional 2D culture methods. There is a need for the online monitoring of such systems to provide better understanding and control of the processes involved and to prevent the disruption of these processes caused by offline sampling and endpoint analysis. We describe a system for the imaging and analysis of cell aggregation, over long periods, within a high aspect rotating vessel (HARV). The system exploits side illumination, using an adjustable beam pattern, to restrict the detected light to that scattered by the cell aggregates, thus eliminating the need for the fluorescent labeling of the cells. The in situ aggregation of mammalian cells (MCF-7 breast carcinoma cells) was monitored over an 8 h period and image sequences showing the growth and motion of the aggregates within the bioreactor were obtained. Detailed size and population data have been derived characterizing the development of the aggregates during this time. We show how the number of resolvable aggregates increases to reach a peak and then declines as these aggregates merge. Once formed, remaining aggregates are found to consolidate to form more tightly packed bodies, typically reducing in cross-sectional area by one third. These results provide the basis for the development of an automated feedback system to control the growth of 3D cell cultures for repeatable, reliable, and quality controlled experimentation.

Comparison of methods for reducing the effects of scattering in spectrophotometry.

Light scattering provides a problem in optical spectroscopy as the relationship between attenuation and absorption in the presence of scattering is nonlinear. Three simple methods of reducing the effects of scattering and hence returning to an approximately linear relationship are considered in this paper, namely, extracting light that has maintained its original polarization state through subtraction of orthogonal polarization states, use of an added absorber, and spatial filtering. These can all be applied relatively easily to conventional spectrophotometers. However, there is an inevitable trade-off between the accuracy of the measurement and the signal-to-noise ratio as scattered light is rejected from the detector. It is demonstrated that polarization subtraction is the most efficient technique at selecting weakly scattered photons from a scattered light background as it enables the relationship between attenuation and absorption coefficient to become more linear while maintaining a higher number of detected photons. In practical use, the drawback of polarization subtraction over added absorber and spatial filtering methods is that a large dc background light level is maintained, which contributes to a higher shot noise. This means that when the scattering coefficient is high (micros > or = 7 mm(-1)) the added absorber method offers better performance for shot noise limited detection.

Application of region-based segmentation and neural network edge detection to skin lesions.

This paper proposes two approaches to the skin lesion image segmentation problem. The first is a mainly region-based segmentation method where an optimal threshold is determined iteratively by an isodata algorithm. The second method proposed is based on neural network edge detection and a rational Gaussian curve that fits an approximate closed elastic curve between the recognized neural network edge patterns. A quantitative comparison of the techniques is enabled by the use of synthetic lesions to which Gaussian noise is added. The proposed techniques are also compared with an established automatic skin segmentation method. It is demonstrated that for lesions with a range of different border irregularity properties the iterative thresholding method provides the best performance over a range of signal to noise ratios. Iterative thresholding technique is also demonstrated to have similar performance when tested on real skin lesions.

Analysis of the spatial distribution of polarized light backscattered from layered scattering media.

The scattering of polarized light from a two layer scattering medium is investigated using Monte Carlo simulations. First order and normalized second order moments are used to analyze the spatial properties of the emerging light in different polarization states. Linearly and circularly polarized illumination is used to probe different depths. Absorption and layer thickness are varied and it is demonstrated that the determination of these values is aided by the inclusion of polarization information. The lateral and depth localization of light by polarization subtraction is also quantified. Potential applications of these techniques are burn depth and melanoma thickness measurements.

Success and future of demography: the role of data and methods.

Demography typifies paradigmatic success; that is, cumulative scientific work that has provided useful perspectives on a set of important questions. This success can be traced partly to the core subject matter of demography, which is relatively conducive to quantitative, observational science. The development of demography was further aided by extrinsic factors, such as the import of its data for government administration, for business purposes, and the import of demographic questions for social problems and public policy. These observations make suspect any simple projection of demography's success into the future or the transport of its experience to other disciplines.

Reexamining the link of early childbearing to marriage and to subsequent fertility.

Using data from the 1980, 1985, and 1990 Current Population Surveys, we show that the link between early fertility and nonmarital births has become stronger. Women who give birth earlier are increasingly likely to be unmarried. In contrast, we find a weaker association between first births at young (versus older) ages and (1) a rapid pace of subsequent childbearing and (2) higher completed fertility. We discuss possible causes and consequences of these changes.

Effects of polarization state and scatterer concentration on optical imaging through scattering media.

The imaging resolution in turbid media is severely degraded by light scattering. Resolution can be improved if the unscattered or weakly scattered light is extracted. Here the state of polarization of the emerging light is used to discriminate photon path length, with the more weakly scattered photons maintaining their original polarization state. It is experimentally demonstrated that over a wide range of scatterer concentrations there exist three distinct imaging regimes. It is also shown that within the intermediate regime one of two distinct imaging techniques is appropriate, depending on the particle size.

Education and the changing age pattern of American fertility: 1963-1989.

Using pooled data from the 1980, 1985, and 1990 Current Population Surveys, we describe fertility trends by age and education for the period 1963-1989. Interest focuses on whether the effects of education have changed across this period. We show that women with college degrees experienced dramatic shifts toward later ages of childbearing. This shift is consistent with arguments we develop about the increased opportunity for women to pursue careers and about changes in the availability of child care.

Racial differences in marriage and childbearing: oral history evidence from the South in the early twentieth century.

Using oral histories collected in 1938 and 1939 in the Southern United States, this article examines how African-Americans and whites viewed marriage and nonmarital childbearing. The authors document distinct racial differences in family norms and the sanctions that supported those norms. Giving birth outside a marital relationship was clearly not the stigmatizing event for African-Americans that it was for whites. The authors also found that African-Americans were more likely than whites to end marriages under similar conditions. These results suggest that debates about contemporary racial differences need to take into account the historical background, both cultural and demographic, of diverse groups.

A decomposition of trends in the nonmarital fertility ratios of blacks and whites in the United States, 1960-1992.

We use a method of standardization and decomposition developed by Das Gupta to update Smith and Cutright's analysis of demographic factors responsible for increases in the nonmarital fertility ratio (illegitimacy ratio) among blacks and whites in the United States. We create standardized rates for each year between 1960 and 1992, and consistent, exhaustive decompositions of the nonmarital fertility ratio for any interval during this period in terms of four components: (1) the age distribution of women of reproductive age, (2) the proportion of women unmarried at each age, (3) the age-specific birth rates of married women, and (4) the age-specific birth rates of unmarried women. Nonmarital fertility ratios are much higher among blacks than among whites, but both increased monotonically from 1960 to 1992. During the last 10 years, each increased by nearly 10 percentage points. Increases in the proportion of women not married, at all ages, account for the preponderance of the increase in black nonmarital fertility ratios. Increasing rates of unmarried childbearing, however, have played a role during the most recent decade (1983-1992). For whites, from 1960 until 1975, declines in marital fertility were most important in producing increases in the proportion of children born out of wedlock. Since then, these proportions have increased primarily because of increases in unmarried women's birth rates, and secondarily because of declines in the proportion of women who are married. These trends are consistent with arguments that emphasize declining economic incentives to marry and reduced access to, and acceptability of, abortion.