Modelling biological invasions: individual to population scales at interfaces

Extracting the population level behaviour of biological systems from that of the individual is critical in understanding dynamics across multiple scales and thus has been the subject of numerous investigations. Here, the influence of spatial heterogeneity in such contexts is explored for interfaces with a separation of the length scales characterising the individual and the interface, a situation that can arise in applications involving cellular modelling. As an illustrative example, we consider cell movement between white and grey matter in the brain which may be relevant in considering the invasive dynamics of glioma. We show that while one can safely neglect intrinsic noise, at least when considering glioma cell invasion, profound differences in population behaviours emerge in the presence of interfaces with only subtle alterations in the dynamics at the individual level. Transport driven by local cell sensing generates predictions of cell accumulations along interfaces where cell motility changes. This behaviour is not predicted with the commonly used Fickian diffusion transport model, but can be extracted from preliminary observations of specific cell lines in recent, novel, cryo-imaging. Consequently, these findings suggest a need to consider the impact of individual behaviour, spatial heterogeneity and especially interfaces in experimental and modelling frameworks of cellular dynamics, for instance in the characterisation of glioma cell motility

Measurement of cone dark adaptation: a comparison of four psychophysical methods

Purpose: Dark adaptometry is an important clinical tool for the diagnosis of a range of conditions, including age-related macular degeneration (AMD). In order to identify the most robust, clinically applicable technique for the measurement of cone dark adaptation, the repeatability and agreement of four psychophysical methods were assessed. Methods: Data were obtained from 31 healthy adults on two occasions, using four psychophysical methods. Participants’ pupils were dilated and 96% of cone photopigment was bleached before threshold was monitored in the dark using one of the techniques, selected at random. This procedure was repeated for each of the remaining methods. An exponential recovery function was fitted to all threshold recovery data. The co-efficient of repeatability (CoR) was calculated to assess the repeatability of the methods and a repeated measures analysis of variance (ANOVA) was used to compare mean recovery parameters. Results: All four methods demonstrated a similar level of inter-session repeatability for measurement of cone recovery, yielding CoRs between 1.18 and 1.56 minutes. There were no statistically significant differences in estimates of mean time constant of cone recovery (cone τ) between the four methods (p = 0.488), however significant differences initial and final cone thresholds were reported (p < 0.005). Conclusions: All of the techniques were capable of monitoring the rapid changes in visual threshold that occur during cone dark adaptation and the repeatability of the techniques was similar. This indicates that, despite the respective advantages and disadvantages of these psychophysical techniques, all four methods would be suitable for measuring cone dark adaptation in clinical practice

The effect of pre-adapting light intensity on dark adaptation in early age-related macular degeneration

Background This study aimed to identify the pre-adapting light intensity that generated the maximum separation in the parameters of dark adaptation between participants with early age-related macular degeneration (AMD) and healthy control participants in the minimum recording time. Methods Cone dark adaptation was monitored in 10 participants with early AMD and 10 age-matched controls after exposure to three pre-adapting light intensities, using an achromatic annulus (12° radius) centred on the fovea. Threshold recovery data were modelled, and the time constant of cone recovery (τ), final cone threshold, and time to rod-cone-break (RCB) were determined. The diagnostic potential of these parameters at all pre-adapting intensities was evaluated by constructing receiver operating characteristic (ROC) curves. Results There were significant differences between those with early AMD and healthy controls in cone τ and time to RCB (p < 0.05) at all pre-adapting ‘bleaching’ intensities. ROC curves showed that the diagnostic potential of dark adaptometry was high following exposure to all three pre-adapting intensities, generating an area under the curve in excess of 0.87 ± 0.08 for cone τ and time to RCB for all conditions. Conclusions Dark adaptation was shown to be highly diagnostic for early AMD across a range of pre-adapting light intensities, and therefore, the lower pre-adapting intensities evaluated in this study may be used to expedite dark adaptation measurement in the clinic without compromising the integrity of the data obtained. This study reinforces the suggestion that cone and rod dark adaptation are good candidate biomarkers for early AMD

Functional Imaging of the Outer Retinal Complex using High Fidelity Imaging Retinal Densitometry

We describe a new technique, high fidelity Imaging Retinal Densitometry (IRD), which probes the functional integrity of the outer retinal complex. We demonstrate the ability of the technique to map visual pigment optical density and synthesis rates in eyes with and without macular disease. A multispectral retinal imaging device obtained precise measurements of retinal reflectance over space and time. Data obtained from healthy controls and 5 patients with intermediate AMD, before and after photopigment bleaching, were used to quantify visual pigment metrics. Heat maps were plotted to summarise the topography of rod and cone pigment kinetics and descriptive statistics conducted to highlight differences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v = 0.043 SD 0.019 min-1 and v = 0.119 SD 0.046 min-1, respectively) were approximately half those observed in healthy controls (v = 0.079 SD 0.024 min-1 for rods and v = 0.206 SD 0.069 min-1 for cones). By mapping visual pigment kinetics across the central retina, high fidelity IRD provides a unique insight into outer retinal complex function. This new technique will improve the phenotypic characterisation, diagnosis and treatment monitoring of various ocular pathologies, including AMD

Predicting Content Views Using Finite Integrals

Video hosting and sharing services enable creators and advertisers to create campaigns that engage viewers. To price the advertisements, and to give advertisers on the campaign an idea of the popularity of the content, the viewership is predicted. Both under- and over-prediction of views are associated with penalties, respectively of wasted inventory and capacity crunches. View estimations based on channel average suffer from sample bias and invisible trends. This disclosure describes techniques of in-flight view prediction, e.g., predictions of views done after the launch of a campaign for the remaining days of a campaign. The predictions of the total views on a line-up of in-flight videos are based on the distributions of prior view history. The described predictor delivers continuously improving predictions for live videos, and enables determination of whether a campaign is meeting view goals. It thereby enables real-time fine-tuning of inventory and capacity for the remaining days of the campaign

How effective is eccentric viewing training? A systematic literature review

Purpose: The global prevalence of age-related macular degeneration (AMD) and associated central vision loss (CVL) is rising. CVL hinders the performance of many activities of daily living (ADLs). Adaptive strategies such as eccentric viewing (EV) and steady eye strategy (SES) may be used to compensate for CVL. In order to establish the potential of these rehabilitation strategies, this systematic review evaluates current literature regarding the effectiveness of EV and SES training in people with CVL. Recent Findings: The search strategies identified 2605 publications, 36 of which met the inclusion criteria for the review, but only three of which were randomised controlled trials. This literature shows that EV and SES training can improve near visual acuity, reading speed, and performance of ADLs in people with CVL. However, there was insufficient literature to establish a relationship between training and distance visual acuity or quality-of-life. There is no conclusive evidence to show that a particular model of EV training is superior to another, little clear evidence of a relationship between participant characteristics and training outcomes and no data regarding the cost effectiveness of training. Summary: This report highlights the need for further robust research to establish the true potential and cost effectiveness of EV and SES training as a rehabilitation strategy for individuals with CVL

The pH-dependence of lipid-mediated antimicrobial peptide resistance in a model Staphylococcal plasma membrane: a two-for-one mechanism of epithelial defence circumvention.

The mechanisms of membrane defence by lysylphosphatidylglycerol (LPG), were investigated using synthetic biomimetic mono- and bilayer models of methicillin resistant S. aureus ST239 TW, based on its lipid composition in both pH 7.4 (28% LPG) and pH 5.5 (51% LPG) cultures. These models incorporated a stable synthetic analogue of LPG (3adLPG) to facilitate long-duration biophysical studies, which were previously limited by the lability native LPG. Both increased 3adLPG content and full headgroup ionization at pH 5.5, increased bilayer order and dampened overall charge, via the formation of neutral ion pairs with anionic lipids. Ion pair formation in air/liquid interface lipid monolayers elicited a significant condensing effect, which correlated with the inhibition of subphase-injected magainin 2 F5W partitioning. In fluid phase lipid vesicles, increasing the proportion of 3adLPG from 28 to 51 mol% completely inhibited the adoption of the membrane-active ?-helical conformation of the peptide, without the need for full headgroup ionization. Neutron reflectivity measurements performed on biomimetic PG/3adLPG fluid floating bilayers, showed a significant ordering effect of mild acidity on a bilayer containing 30 mol% 3adLPG, whilst peptide binding/partitioning was only fully inhibited in a bilayer with 55 mol% 3adLPG at pH 5.5. These findings are discussed with respect to the roles of LPG in resistance to human epithelial defences in S. aureus and the continued evolution of this opportunistic pathogen’s virulence

Soot reduction in diesel engines by catalytic effects

Recent tests at Brookhaven National Laboratory indicate that both small additions of alcohols to the fuel and the presence of platinum surfaces in the combustion chamber can reduce soot emissions in a diesel engine. These tests were conducted over a limited range of operation in a single cylinder CFR engine. Most of the testing was done using pure cetane as a fuel at constant speed and load. Possible major features of the reaction mechanisms for both fuel additives and surface catalyst effectiveness are presented