Automated tumor analysis for molecular profiling in lung cancer

The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics.

Channel Measurements of Device-to-Device Communications at 2.45 GHz

In the future, device-to-device communications will become a fundamental part of cellular communications. Interoperability between handsets will be facilitated using frequencies located in a number of bands including those found in the Industrial, Scientific and Medical (ISM) band at 2.45 GHz. In this paper, we present the results of channel measurements made between two hypothetical cellular handsets operating at 2.45 GHz in an outdoor environment. We consider a range of typical usage scenarios such as both user equipment being held at the head while imitating a voice call, placed in user's pocket for both stationary and dynamic links. A range of parameter estimates obtained using the shadowed κ-μ fading model are also presented.

Fading Characteristics of Body–to–Body Channels Subject to Vehicular Traffic Conditions at 2.45 GHz

In this paper we investigate the small-scale fading characteristics of body-to-body communications channels in an urban environment at 2.45 GHz. The experiments considered body-to-body channels between devices positioned on two persons on either side of a busy road. The Ricean-K factors estimated from the measurements suggest that a significant dominant component existed in the majority of the channels.

Vehicular Traffic Intersecting Body-to-Body Communications Channels at 2.45 GHz

In this paper we investigate the effects of vehicular traffic on body-to-body (B2B) communications channels in an urban environment at 2.45 GHz. In particular, the impact of differing vehicle types passing in the vicinity of a B2B link are investigated for different body orientations relative to one another at the side of a busy urban street. Initial findings suggest that the average disturbance in a B2B channel can last for 2 seconds and depending on the vehicle size, fades in excess of 40 dB can occur. The body orientations are shown to be a significant factor on the effects of vehicular traffic on the B2B channel.

Simultaneous Measurements of the Channel Response for Multiple Eavesdroppers Operating in the Vicinity of a Body Area Network at 2.45 GHz

Channel randomness can be exploited to generate secret keys. However, to ensure secrecy, it is necessary that the channel response of any eavesdropping party remain sufficiently de-correlated with that of the legitimate users'. In this paper, we investigate whether such de-correlation occurs for a body area network (BAN) operating in an indoor environment at 2.45 GHz. The hypothetical BAN configuration consisted of two legitimate transceivers, one situated on the user's left wrist and the other on the user's waist. The eavesdroppers were positioned in either a co-located or distributed manner in the area surrounding the BAN user. Using the simultaneous channel response measured at the legitimate BAN nodes and the eavesdropper positions for stationary and mobile scenarios, we analyze the localized correlation coefficient. This allows us to determine if it is possible to generate secret keys in the presence of multiple eavesdroppers in an indoor environment. Our experimental results show that although channel reciprocity was observed for both the stationary and the mobile scenarios, a higher de-correlation between the legitimate users' channels was observed for the stationary case. This indicates that mobile scenarios are better suited for secret key generation.

Signal Reception Characteristics in the Proximity of Alice and Bob for Secure Indoor Peer-to-Peer Communications At 2.45 GHz

Mutual variation of the received signal which occurs as a consequence of the channel reciprocity property has recently been proposed as a viable method for secret key generation. However, this cannot be strictly maintained in practice as the property is applicable only in the absence of interference. To ensure the propagation defined key remains secret, one requirement is that there remain high degrees of uncertainty between the legitimate users channel response and that of any eavesdropper's. In this paper, we investigate whether such de-correlation occurs for an indoor point-to-point link at 2.45 GHz. This is achieved by computing the localized correlation coefficient between the simultaneous channel response measured by the legitimate users and that of multiple distributed eavesdroppers for static and dynamic scenarios.

A Community Driven Approach to Reconstruction Management

Without human beings, and human activities, hazards can strike but disasters cannot occur, they are not just natural phenomena but a social event (Van Der Zon, 2005). The rapid demand for reconstruction after disastrous events can result in the impacts of projects not being carefully considered from the outset and the opportunity to improve long-term physical and social community structures being neglected. The events that struck Banda Aceh in 2004 have been described as
a story of ‘two tsunamis’, the first being the natural hazard that struck and the second being the destruction of social structures that occurred as a result of unplanned, unregulated and uncoordinated response (Syukrizal et al, 2009). Measures must be in place to ensure that, while aiming to meet reconstruction
needs as rapidly as possible, the risk of re-occurring disaster impacts are reduced through both the physical structures and the capacity of the community who inhabit them. The paper explores issues facing reconstruction in a post-disaster scenario, drawing on the connections between physical and social reconstruction in order to address long term recovery solutions. It draws on a study of relevant literature and a six week pilot study spent in Haiti exploring the progress of recovery in the Haitian capital and the limitations still restricting reconstruction efforts. The study highlights the need for recovery management strategies that recognise the link between social and physical reconstruction and the significance of community based initiatives that see local residents driving recovery in terms of debris handling and rebuilding. It demonstrates how a community driven approach to physical reconstruction could also address the social impacts of events that, in the case of places such as Haiti, are still dramatically restricting recovery efforts.

An optimized reverse-phase high performance liquid chromatographic method for evaluating percutaneous absorption of glucosamine hydrochloride

A relatively simple, selective, precise and accurate high performance liquid chromatography (HPLC) method based on a reaction of phenylisothiocyanate (PITC) with glucosamine (GL) in alkaline media was developed and validated to determine glucosamine hydrochloride permeating through human skin in vitro. It is usually problematic to develop an accurate assay for chemicals traversing skin because the excellent barrier properties of the tissue ensure that only low amounts of the material pass through the membrane and skin components may leach out of the tissue to interfere with the analysis. In addition, in the case of glucosamine hydrochloride, chemical instability adds further complexity to assay development. The assay, utilising the PITC-GL reaction was refined by optimizing the reaction temperature, reaction time and PITC concentration. The reaction produces a phenylthiocarbamyl-glucosamine (PTC-GL) adduct which was separated on a reverse-phase (RP) column packed with 5 microm ODS (C18) Hypersil particles using a diode array detector (DAD) at 245 nm. The mobile phase was methanol-water-glacial acetic acid (10:89.96:0.04 v/v/v, pH 3.5) delivered to the column at 1 ml min-1 and the column temperature was maintained at 30 degrees C. Galactosamine hydrochloride (Gal-HCl) was used as an internal standard. Using a saturated aqueous solution of glucosamine hydrochloride, in vitro permeation studies were performed at 32+/-1 degrees C over 48 h using human epidermal membranes prepared by a heat separation method and mounted in Franz-type diffusion cells with a diffusional area 2.15+/-0.1 cm2. The optimum derivatisation reaction conditions for reaction temperature, reaction time and PITC concentration were found to be 80 degrees C, 30 min and 1% v/v, respectively. PTC-Gal and GL adducts eluted at 8.9 and 9.7 min, respectively. The detector response was found to be linear in the concentration range 0-1000 microg ml-1. The assay was robust with intra- and inter-day precisions (described as a percentage of relative standard deviation, %R.S.D.) <12. Intra- and inter-day accuracy (as a percentage of the relative error, %RE) was <or=-5.60 and <or=-8.00, respectively. Using this assay, it was found that GL-HCl permeates through human skin with a flux 1.497+/-0.42 microg cm-2 h-1, a permeability coefficient of 5.66+/-1.6x10(-6) cm h-1 and with a lag time of 10.9+/-4.6 h.

Efficacy and Acceptability of Reduced Intensity Constraint-Induced Movement Therapy for Children Aged 9–11 years with Hemiplegic Cerebral Palsy: A Pilot Study

OBJECTIVE: Assess efficacy and acceptability of reduced intensity constraint-induced movement therapy (CIMT) in children with cerebral palsy (CP).

METHODS: Single-subject research design and semi-structured interviews. Children (9-11y) with hemiplegia underwent five baseline assessments followed by two weeks CIMT. Six further assessments were performed during treatment and follow-up phases. The primary outcome was the Melbourne Assessment of Unilateral Upper Limb Function (MUUL). Quantitative data were analysed using standard single-subject methods and qualitative data by thematic analysis.

RESULTS: Four of the seven participants demonstrated statistically significant improvements in MUUL (3-11%, p < .05). Two participants achieved significant improvements in active range of motion but strength and tone remained largely unchanged. Qualitative interviews highlighted limitations of the restraint, importance of family involvement, and coordination of treatment with education.

CONCLUSIONS: Reduced intensity CIMT may be effective for some children in this population; however it is not suitable for all children with hemiplegia.