Expression of proliferation-dependent antigens during cellular ageing of normal and progeroid human fibroblasts

Normal human fibroblasts display a limited lifespan in culture, which is due to a steadily decreasing fraction of cells that are able to proliferate. Using antibodies that react with antigens present in proliferating cells only, in an indirect immunofluorescence assay, we have estimated the fraction of proliferating cells in cultures of normal human fibroblasts. Furthermore, we have estimated the rate of decline in the fraction of proliferating cells during the process of cellular ageing by application of the assay to normal human fibroblasts throughout their lifespan in culture. Werner’s Syndrome is an autosomal recessive disease in which individuals display symptoms of ageing prematurely. Werner’s Syndrome fibroblasts display a reduced lifespan in culture compared with normal human fibroblasts. Like normal human fibroblasts, the growth of Werner’s Syndrome fibroblasts is characterised by a decreasing fraction of cells reacting with the proliferationassociated antibodies throughout their lifespan in culture. However, the rate of loss of proliferating cells in Werner’s Syndrome fibroblasts during the process of cellular ageing is accelerated 5- to 6-fold compared with the rate determined for normal human fibroblasts

Hydroxyapatite promotes superior adhesion and proliferation of telomerase transformed keratocytes in comparison with inert plastic skirt materials used in leading contemporary keratoprostheses

Aim: Published clinical series suggest the osteoodontokeratoprosthesis (OOKP) may have a lower extrusion rate than current synthetic keratoprostheses. The OOKP is anchored in the eye wall by autologous tooth. The authors’ aim was to compare adhesion, proliferation, and morphology for telomerase transformed keratocytes seeded on calcium hydroxyapatite (the principal mineral constituent of tooth) and materials used in the anchoring elements of commercially available synthetic keratoprostheses. Methods: Test materials were hydroxyapatite, polytetrafluoroethylene (PTFE), polyhydroxyethyl methacrylate (HEMA), and glass (control). Cell adhesion and viability were quantified at 4 hours, 24 hours, and 1 week using a calcein-AM/EthD-1 viability/cytotoxicity assay. Focal contact expression and cytoskeletal organisation were studied at 24 hours by confocal microscopy with immunoflourescent labelling. Further studies of cell morphology were performed using light and scanning electron microscopy. Results: Live cell counts were significantly greater on hydroxyapatite surfaces at each time point (p<0.04). Dead cell counts were significantly higher for PTFE at 7 days (p<0.002). Β1 integrin expression was highest on hydroxyapatite. Adhesion structures were well expressed in flat, spread out keratocytes on both HA and glass. Keratocytes tended to be thinner and spindle shaped on PTFE. The relatively few keratocytes visible on HEMA test surfaces were rounded and poorly adherent. Conclusions: Keratocyte adhesion, spreading, and viability on hydroxyapatite test surfaces is superior to that seen on PTFE and HEMA. Improving the initial cell adhesion environment in the skirt element of keratoprostheses may enhance tissue integration and reduce device failure rates

A New Approach to Better Low-Cost MEMS IMU Performance Using Sensor Arrays

Over the past decade and a half, the combination of low-cost, lightweight micro-electro-mechanical sensors (MEMS) technology and multisensor integration has enabled inertial sensors to be deployed over a much wider range of navigation applications [1]. Examples include pedestrian dead-reckoning using step detection technology [2, 3], aiding of GNSS signal tracking during jamming [4, 5], and simultaneous localisation and mapping (SLAM) using radio signals [6]. However, for best performance, a MEMS inertial measurement unit (IMU) must be calibrated in the laboratory prior to use, which increases the cost by more than $1000 per unit. In this paper, we examine and present a range of techniques which use an array of inexpensive MEMS sensors to improve the performance of a MEMS IMU without requiring a full calibration prior to use. As the cost of calibration of a high-performance MEMS IMU far outweighs the cost of the hardware, there is considerable scope to improve the performance by adding additional sensors, before the cost of the IMU reaches that of a laboratory calibrated equivalent. Combining MEMS IMUs in an array has been studied before. However, the most common approach was simply to take an average of the input of several identical sensors [7]. If the sensor errors were independent, this could be expected to improve performance by a factor of root-n where, n is the number of IMUs combined. In this paper more sophisticated techniques are investigated that use knowledge of the sensor characteristics to obtain better performance. Three different properties of MEMS sensors may potentially be exploited: 1) The common-mode errors of different sensors of the same design; 2) The different characteristics of in-plane and out-of-plane sensors; and 3) The complementary properties of MEMS sensors with different dynamic ranges. In [8], it is shown that different individual sensors of the same design exhibit similar bias variation with temperature and that improved accuracy may be obtained by differencing the outputs of two gyroscopes mounted with their sensitive axes in opposing directions. Here, this approach will be independently verified and the performance benefits assessed with a range of different MEMS accelerometers and gyros, including Bosch BMA180 accelerometers, Analogue Devices ADXL345 accelerometers, ST Microtronics L3G4200D gyroscopes. Preliminary indications are that there is considerable common bias variation with temperature for the in-plane sensors of L3G4200D gyroscopes, and some common mode behaviour for the low-cost accelerometers. The second idea presented is exploiting the differences between the in-plane and out-of-plane axis outputs of single-chip inertial sensor triads, to improve the performance of an array-based IMU. Early experiment s point to considerable differences between the two which could markedly affect navigation performance. Both accelerometer and gyro triads can exhibit smaller errors from the in-plane sensors than from the out-of-plane sensors. Therefore, experiments were conducted using mutually-perpendicular arrays of accelerometer and gyro triads to determine whether better performance could be obtained using only the in-plane sensors. The third idea is to combine the outputs of MEMS sensors with different dynamic ranges to exploit the lower noise exhibited by some lower-dynamic-range sensors compared to their higher-dynamic-range counterparts. The sensor outputs are thus weighted according to the platform dynamics. That is, predominantly using the high-precision sensor when dynamics are low and using the full-range sensor when the dynamics are high. Several versions of this weighted signal combination will be presented and compared. Early indications are that there can be a significant benefit in this approach for some sensor designs, but not others. Finally, this paper will also examine the efficacy of a once-only static calibration on purchase, performed by the user instead of the supplier, for improving navigation performance. It is essential for a user-performed calibration that the physical movements required of the sensor are very simple and easily understood and completed, even if the underlying method is complex. To this end data, recorded on different days from an array of MEMS sensors within a precisely manufactured rapid prototyped ‘calibration cube’, will be analysed. These measurements are taken at precisely orthogonal angles of the cubes six faces, and allow the scale factor errors, biases and axes alignments of the accelerometers to be determined. The computed calibration corrections over several days will be compared to enable the efficacy of the one-time calibration technique to be assessed. The development of a full calibration routine will be the subject of future research. In summary, this paper will present several new methods for utilising the output of an array of low-cost sensors to improve the performance of a MEMS IMU, and also expands on methods proposed in existing research. As uncalibrated MEMS IMUs are of low performance there is a great potential for new applications if the performance can be improved closer to the level of those which are factory calibrated. / References [1] Groves, P. D., Principles of GNSS, inertial, and multi-sensor integrated navigation systems, Second Edition, Artech House, 2013. [2] Gustafson, D., J. Dowdle, and K. Flueckiger, “A Deeply Integrated Adaptive GPS-Based Navigator with Extended Range Code Tracking,” Proc. IEEE PLANS 2000. [3] Groves, P. D., C. J. Mather and A. A. Macaulay, “Demonstration of Non-Coherent Deep INS/GPS Integration for Optimized Signal to Noise Performance,” Proc. ION GNSS 2007. [4] Ma, Y., W. Soehren, W. Hawkinson, and J. Syrstad, "An Enhanced Prototype Personal Inertial Navigation System," Proc. ION GNSS 2012. [5] Groves, P. D., et al., “Inertial Navigation Versus Pedestrian Dead Reckoning: Optimizing the Integration,” Proc. ION GNSS 2007. [6] Faragher, R. M., C. Sarno, and M. Newman, “Opportunistic Radio SLAM for Indoor Navigation using Smartphone Sensors,” Proc. IEEE/ION PLANS 2012. [7] Bancroft, J. B., and G. Lachapelle, “Data fusion algorithms for multiple inertial measurement units,” Sensors, Vol. 11, No. 7, 2011, pp. 6771-6798. [8] Yuksel, Y., N. El-Sheimy, N., and A. Noureldin, “Error modelling and characterization of environmental effects for low cost inertial MEMS units,” Proc. IEEE/ION PLANS 2010

The impact of rapid malaria diagnostic tests upon anti-malarial sales in community pharmacies in Gwagwalada, Nigeria

Background Rapid diagnostics tests for malaria (RDT) have become established as a practical solution to the challenges of parasitological confirmation of malaria before treatment in the public sector. However, little is known of their impact in private health sector facilities, such as pharmacies and drug shops. This study aimed to assess the incidence of malaria among unwell patients seeking anti-malarial treatment in two community pharmacies in Nigeria and measure the impact RDTs have on anti-malarial sales. Methods This was a comparison study of two pharmacies located in the suburbs of Gwagwalada, in the Federal Capital Territory of Nigeria, between May and July 2012. In the intervention arm, patients seeking to purchase anti-malarials had an RDT performed before treatment while the control pharmacy continued normal routine practice. Results A total of 1,226 participants were enrolled into the study. The incidence of malaria in the intervention arm (n = 619) was 13.6% and adolescent participants had a statistically significant higher incidence (26.0%) compared to adults (11.9%) (P = 0.001). A history of fever in the last 48 hours was associated with a statistically significant higher incidence of malaria (28.3%) (P < 0.001). Having a RDT test reduced the chance of purchasing an anti-malarial by 42% (95% CI: 38%-46%) compared to not having a test. 51.6% (276) of the study participants with a RDT negative result still purchased anti-malarials, especially if anti-malarials had been recommended by a health professional (58.9%) compared to self-referral (44.2%) (P = 0.001). Patients with RDT negative results were also more likely to purchase an anti-malarial if there was a reported malaria positive laboratory test prior to presentation (66.2%; P = 0.007), a history of fever in the last 48 hours (60.5%; P = 0.027), and primary school education or less (69.4%; P = 0.009). After adjusting for age group and gender differences, having at least a secondary school education reduced the chance of buying an anti-malarial (OR 0.504 (95% CI: 0.256-0.993)) compared to having primary education or lower. Conclusion The study highlights the enormous potential for improving appropriate prescription of anti-malarials in pharmacies and preventing unnecessary use of artemisinin combination therapy (ACT)

Developing retinal biomarkers of neurological disease: an analytical perspective

The inaccessibility of the brain poses a problem for neuroscience. Scientists have traditionally responded by developing biomarkers for brain physiology and disease. The retina is an attractive source of biomarkers since it shares many features with the brain. Some even describe the retina as a ‘window’ to the brain, implying that retinal signs are analogous to brain disease features. However, new analytical methods are needed to show whether or not retinal signs really are equivalent to brain abnormalities, since this requires greater evidence than direct associations between retina and brain. We, therefore propose a new way to think about, and test, how clearly one might see the brain through the retinal window, using cerebral malaria as a case study

Soroban: Attributing latency in virtualized environments

Applications running in the cloud have highly-variable response times due to the lack of perfect performance isolation from other services served by common infrastructure. In particular, response latency when executing on a loaded hypervisor or in a container is substantially higher than uncontested bare-metal performance. Whilst efforts to increase performance isolation continue, we present Soroban, a framework for attributing latency to either the cloud provider or their customer. Soroban allows cloud providers to instrument commonly used programs, such as a web server to determine, for each request, how much of the latency is due to the cloud provider, or the consumer. We apply Soroban to a HTTP server and show that it identifies when the cause of latency is due to a provider-induced activity, such as underprovisioning a host, or due to the software run by the customer.This is the author accepted manuscript. The final version is available from USENIX. via https://www.usenix.org/conference/hotcloud15/workshop-program/presentation/sne

Automated counting for Plasmodium falciparum cytoadherence experiments.

The automated counting programs are an accurate and practical way of quantifying static parasite binding assays to purified proteins. They are less accurate when applied to cell based systems, but can still provide a reasonable level of accuracy to give a semi-quantitative readout