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.

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.

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.

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.

The UNIX Operating System: A Model for Software Design.

The UNIX operating system, a general-purpose time-sharng system, has, without marketing, advertising, or technical support, become widely used by universities and scientific research establishments. It is the de facto standard of comparison for such systems and has spawned a small industry of suppliers of UNIX variants and look-alikes. This article attempts to uncover the reasons for its success and to draw some lessons for the future of operating systems.

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.

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.

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.

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.

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).

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.

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.

Melanotic ameloblastoma (retinal anlage tumour) of the skull in a Nigerian child.

An unusually large melanotic neuroectodermal (retinal anlage) tumour of the frontal bone is described in a Nigerian child. It is the first instance of involvement of the skull by this disease seen in 20 years at the University College Hospital, Ibadan, Nigeria.

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.

The transition to motherhood: the intersection of structural and temporal dimensions.

PIP: Prior work on the determinants of the 1st-birth process can be divided into 3 approaches: 1) time-series analysis focusing on description and determinants of trends; 2) cross-sectional studies examing childlessness or adolescent fertility; and 3) life-course studies dealing with the timing of fertility relative to other events. Drawing on these traditions, the conceptual framework places the 1st-birth process within, respectively, an aggregate-time dimension indicated by period or cohort, an individual-time dimension indicatedd by the respondent's age, and a social-structural dimension indicated by the respondent's spanning the 1955-1976 period, and examining conditional birth probabilities, the analysis incorporates each of these dimensions. Each dimension is important. Aggregate time exerts powerful and pervasive effects. Socio-structural variables have nonproportinal effects--tht is, their effects vary with time. The effects of the social-structural variables tend not to interact with the aggregate-time dimension. Finally, predictive power generally declines with inndividual time.^ieng

A comparison of three methods of managing fever in the neurologic patient.

Patients with neurological dysfunction can suffer fevers due to irritation of, or damage to the temperature-regulating center in the brain, or a combination of both. Although hypothermic therapy is a critical treatment nurses often perform, the most effective cooling method has not been studied in the neurological patient. The purpose of this quasi-experimental study was to compare the effectiveness of three methods of fever reduction, and the effect of each on patient shivering. Twenty-one adult febrile neurological patients were randomly placed in one of three temperature reduction groups. One of the temperature reduction protocols was initiated when a subject first became febrile. Rectal temperatures were taken every 15 minutes using an IVAC Temp-Plus thermometer until the subject's temperature returned to 100 degrees F. Subjects were observed for shivering throughout the procedures. The mean time necessary for the subject's temperature to return to 100 degrees F was calculated. A one-way analysis of variance of the time required to reach 100 degrees F was done to determine if a significant difference existed in rate of temperature reduction among the groups. The analysis revealed no statistically significant difference among the three methods, but a chi-square analysis indicated a significant relationship between shivering and the use of a hypothermia blanket.

Predicting childlessness for recent cohorts of American women.

Over 50% of the American women now in the midst of the childbearing years have never borne a child. These levels of childlessness for women in their 20s are the highest ones in a time series that spans most of the twentieth century. Will postponed parenthood be translated into very high levels of permanent childlessness? Or will these cohorts "catch-up" with a late fertility flurry in their 30s and 40s? The authors examine 3 projection strategies: one using women's stated fertility expectations, a second relying on the patterns of previous cohorts, and a third which posits that current rates will persist into the future. The predictive validity of these different projection strategies are tested with data for the 1980-87 period. They show that the projection based on current period rates performs well. Further, the authors argue that it better captures the first birth process than other models. They forecast levels of 20% childless for cohorts of white women born in the early 1960s. Recent trends for nonwhites are very different from those for whites: levels of 4% are forecast for nonwhite women.

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.

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.