Real-time assessment of nanoparticle-mediated antigen delivery and cell response

Nanomaterials are increasingly being developed for applications in biotechnology, including the delivery of therapeutic drugs and of vaccine antigens. However, there is a lack of screening systems that can rapidly assess the dynamics of nanoparticle uptake and their consequential effects on cells. Established in vitro approaches are often carried out on a single time point, rely on time-consuming bulk measurements and are based primarily on populations of cell lines. As such, these procedures provide averaged results, do not guarantee precise control over the delivery of nanoparticles to cells and cannot easily generate information about the dynamics of nanoparticle-cell interactions and/or nanoparticle-mediated compound delivery. Combining microfluidics and nanotechnology with imaging techniques, we present a microfluidic platform to monitor nanoparticle uptake and intracellular processing in real-time and at the single-cell level. As proof-of-concept application, the potential of such a system for understanding nanovaccine delivery and processing was investigated and we demonstrate controlled delivery of ovalbumin-conjugated gold nanorods to primary dendritic cells. Using time-lapse microscopy, our approach allowed monitoring of uptake and processing of nanoparticles across a range of concentrations over several hours on hundreds of single-cells. This system represents a novel application of single-cell microfluidics for nanomaterial screening, providing a general platform for studying the dynamics of cell-nanomaterial interactions and representing a cost-saving and time-effective screening tool for many nanomaterial formulations and cell types

Extra patient movement during mammographic imaging : an experimental study

Objectives: To determine if movement external to the patient occurring during mammography may be a source of image blur. Methods: Four mammography machines with seven flexible and nine fixed paddles were evaluated. In the first stage, movement at the paddle was measured mechanically using two calibrated linear potentiometers. A deformable breast phantom was used to mimic a female breast. For each paddle, the movement in millimeters and change in compression force in Newton was recorded at 0.5 and 1 second intervals respectively for 40 seconds with the phantom in an initially compressed state under a load of 80N. In the second stage, clinical audit on 28 females was conducted on one mammography machine with the 18x24cm and 24x29cm flexible paddles. Results: Movement at the paddle followed an exponential decay with a settling period of approximately 40 seconds. The compression force readings for both fixed and flexible paddles decreased exponentially with time while fixed paddles have a larger drop in compression force than flexible paddles. There is a linear relationship between movement at the paddle and change in compression force. Conclusions: Movement measured at the paddle during an exposure can be represented by a second order system. The amount of extra-patient movement during the actual exposure can be estimated using the linear relationship between movement at the paddle and the change in compression force. Advances in knowledge: This research provides a possible explanation to mammography image blurring caused by extra patient movement and proposes a theoretical model to analyze the movement

Working directly with probabilities in quantum field theory

We present a novel approach to computing transition probabilities in quantum field theory, which allows them to be written directly in terms of expectation values of nested commutators and anti-commutators of field operators, rather than squared matrix elements. We show that this leads to a diagrammatic expansion in which the retarded propagator plays a dominant role. As a result, one is able to see clearly how faster-than-light signalling is prevented between sources and detectors. Finally, we comment on potential implications of this approach for dealing with infra-red divergences

An updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013-2018

Introduction: The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods: We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population-based cancer registry and pathology report data, 2013-18. Results: Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013-18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013-18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013-18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non-melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions: We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential

Effect of simplicity and attractiveness on route selection for different journey types

This study investigated the effects of six attributes, associated with simplicity or attractiveness, on route preference for three pedestrian journey types (everyday, leisure and tourist). Using stated choice preference experiments with computer generated scenes, participants were asked to choose one of a pair of routes showing either two levels of the same attribute (experiment 1) or different attributes (experiment 2). Contrary to predictions, vegetation was the most influential for both everyday and leisure journeys, and land use ranked much lower than expected in both cases. Turns ranked higher than decision points for everyday journeys as predicted, but the positions of both were lowered by initially unranked attributes. As anticipated, points of interest were most important for tourist trips, with the initially unranked attributes having less influence. This is the first time so many attributes have been compared directly, providing new information about the importance of the attributes for different journeys. © 2014 Springer International Publishing

Housing Conditions Differentially Affect Physiological and Behavioural Stress Responses of Zebrafish, as well as the Response to Anxiolytics

Zebrafish are a widely utilised animal model in developmental genetics, and owing to recent advances in our understanding of zebrafish behaviour, their utility as a comparative model in behavioural neuroscience is beginning to be realised. One widely reported behavioural measure is the novel tank-diving assay, which has been often cited as a test of anxiety and stress reactivity. Despite its wide utilisation, and various validations against anxiolytic drugs, reporting of pre-test housing has been sparse in the literature. As zebrafish are a shoaling species, we predicted that housing environment would affect their stress reactivity and, as such, their response in the tank-diving procedure. In our first experiment, we tested various aspects of housing (large groups, large groups with no contact, paired, visual contact only, olfactory contact only) and found that the tank diving response was mediated by visual contact with conspecifics. We also tested the basal cortisol levels of group and individually housed fish, and found that individually housed individuals have lower basal cortisol levels. In our second experiment we found ethanol appeared to have an anxiolytic effect with individually housed fish but not those that were group housed. In our final experiment, we examined the effects of changing the fishes' water prior to tank diving as an additional acclimation procedure. We found that this had no effect on individually housed fish, but appeared to affect the typical tank diving responses of the group housed individuals. In conclusion, we demonstrate that housing represents an important factor in obtaining reliable data from this methodology, and should be considered by researchers interested in comparative models of anxiety in zebrafish in order to refine their approach and to increase the power in their experiments

Escherichia coli O157:H7 in Feral Swine near Spinach Fields and Cattle, Central California Coast1

We investigated involvement of feral swine in contamination of agricultural fields and surface waterways with Escherichia coli O157:H7 after a nationwide outbreak traced to bagged spinach from California. Isolates from feral swine, cattle, surface water, sediment, and soil at 1 ranch were matched to the outbreak strain

Full scale pedestrian impact testing with PMHS: A pilot study

The complexity of vehicle-pedestrian collisions necessitates extensive validation of pedestrian computational models. While body components can be individually simulated, overall validation of human pedestrian models requires full-scale testing with post mortem human surrogates (PMHS). This paper presents the development of a full-scale pedestrian impact test plan and experimental design, and some results from a pilot experiment. The test plan and experimental design are developed based on the analysis of a combination of literature review, multi-body modeling, and epidemiologic studies. The proposed system has proven effective in testing an anthropometrically correct rescue dummy in multiple instances, and in one test with a PMHS.Postprint (published version

Connecting Earth observation to high-throughput biodiversity data

Understandably, given the fast pace of biodiversity loss, there is much interest in using Earth observation technology to track biodiversity, ecosystem functions and ecosystem services. However, because most biodiversity is invisible to Earth observation, indicators based on Earth observation could be misleading and reduce the effectiveness of nature conservation and even unintentionally decrease conservation effort. We describe an approach that combines automated recording devices, high-throughput DNA sequencing and modern ecological modelling to extract much more of the information available in Earth observation data. This approach is achievable now, offering efficient and near-real-time monitoring of management impacts on biodiversity and its functions and services