Immune-Mediated Retinal Vasculitis in Posterior Uveitis and Experimental Models: The Leukotriene (LT)B4-VEGF Axis

Retinal vascular diseases have distinct, complex and multifactorial pathogeneses yet share several key pathophysiological aspects including inflammation, vascular permeability and neovascularisation. In non-infectious posterior uveitis (NIU), retinal vasculitis involves vessel leakage leading to retinal enlargement, exudation, and macular oedema. Neovascularisation is not a common feature in NIU, however, detection of the major angiogenic factor—vascular endothelial growth factor A (VEGF-A)—in intraocular fluids in animal models of uveitis may be an indication for a role for this cytokine in a highly inflammatory condition. Suppression of VEGF-A by directly targeting the leukotriene B4 (LTB4) receptor (BLT1) pathway indicates a connection between leukotrienes (LTs), which have prominent roles in initiating and propagating inflammatory responses, and VEGF-A in retinal inflammatory diseases. Further research is needed to understand how LTs interact with intraocular cytokines in retinal inflammatory diseases to guide the development of novel therapeutic approaches targeting both inflammatory mediator pathways

3D Laser-and-tissue Agnostic Data-driven Method for Robotic Laser Surgical Planning

In robotic laser surgery, shape prediction of an one-shot ablation cavity is an important problem for minimizing errant overcutting of healthy tissue during the course of pathological tissue resection and precise tumor removal. Since it is difficult to physically model the laser-tissue interaction due to the variety of optical tissue properties, complicated process of heat transfer, and uncertainty about the chemical reaction, we propose a 3D cavity prediction model based on an entirely data-driven method without any assumptions of laser settings and tissue properties. Based on the cavity prediction model, we formulate a novel robotic laser planning problem to determine the optimal laser incident configuration, which aims to create a cavity that aligns with the surface target (e.g. tumor, pathological tissue). To solve the one-shot ablation cavity prediction problem, we model the 3D geometric relation between the tissue surface and the laser energy profile as a non-linear regression problem that can be represented by a single-layer perceptron (SLP) network. The SLP network is encoded in a novel kinematic model to predict the shape of the post-ablation cavity with an arbitrary laser input. To estimate the SLP network parameters, we formulate a dataset of one-shot laser-phantom cavities reconstructed by the optical coherence tomography (OCT) B-scan images for the data-driven modelling. To verify the method. The learned cavity prediction model is applied to solve a simplified robotic laser planning problem modelled as a surface alignment error minimization problem. The initial results report (91.1 +- 3.0)% 3D-cavity-Intersection-over-Union (3D-cavity-IoU) for the 3D cavity prediction and an average of 97.9% success rate for the simulated surface alignment experiments

American Exceptionalism: Population Trends and Flight Initiation Distances in Birds from Three Continents

Background All organisms may be affected by humans' increasing impact on Earth, but there are many potential drivers of population trends and the relative importance of each remains largely unknown. The causes of spatial patterns in population trends and their relationship with animal responses to human proximity are even less known. Methodology/Principal Finding We investigated the relationship between population trends of 193 species of bird in North America, Australia and Europe and flight initiation distance (FID); the distance at which birds take flight when approached by a human. While there is an expected negative relationship between population trend and FID in Australia and Europe, we found the inverse relationship for North American birds; thus FID cannot be used as a universal predictor of vulnerability of birds. However, the analysis of the joint explanatory ability of multiple drivers (farmland breeding habitat, pole-most breeding latitude, migratory habit, FID) effects on population status replicated previously reported strong effects of farmland breeding habitat (an effect apparently driven mostly by European birds), as well as strong effects of FID, body size, migratory habit and continent. Farmland birds are generally declining. Conclusions/Significance Flight initiation distance is related to population trends in a way that differs among continents opening new research possibilities concerning the causes of geographic differences in patterns of anti-predator behavior

Variation at the DRD4 locus is associated with wariness and local site selection in urban black swans

BACKGROUND: Interactions between wildlife and humans are increasing. Urban animals are often less wary of humans than their non-urban counterparts, which could be explained by habituation, adaptation or local site selection. Under local site selection, individuals that are less tolerant of humans are less likely to settle in urban areas. However, there is little evidence for such temperament-based site selection, and even less is known about its underlying genetic basis. We tested whether site selection in urban and non-urban habitats by black swans (Cygnus atratus) was associated with polymorphisms in two genes linked to fear in animals, the dopamine receptor D4 (DRD4) and serotonin transporter (SERT) genes. RESULTS: Wariness in swans was highly repeatable between disturbance events (repeatability = 0.61) and non-urban swans initiated escape from humans earlier than urban swans. We found no inter-individual variation in the SERT gene, but identified five DRD4 genotypes and an association between DRD4 genotype and wariness. Individuals possessing the most common DRD4 genotype were less wary than individuals possessing rarer genotypes. As predicted by the local site selection hypothesis, genotypes associated with wary behaviour were over three times more frequent at the non-urban site. This resulted in moderate population differentiation at DRD4 (FST = 0.080), despite the sites being separated by only 30 km, a short distance for this highly-mobile species. Low population differentiation at neutrally-selected microsatellite loci and the likely occasional migration of swans between the populations reduces the likelihood of local site adaptations. CONCLUSION: Our results suggest that wariness in swans is partly genetically-determined and that wary swans settle in less-disturbed areas. More generally, our findings suggest that site-specific management strategies may be necessary that consider the temperament of local animals

The Pandora multi-algorithm approach to automated pattern recognition in LAr TPC detectors

The development and operation of Liquid Argon Time Projection Chambers (LAr TPCs) for neutrino physics has created a need for new approaches to pattern recognition, in order to fully exploit the superb imaging capabilities offered by this technology. The Pandora Software Development Kit provides functionality to aid the process of designing, implementing and running pattern recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition: individual algorithms each address a specific task in a particular topology; a series of many tens of algorithms then carefully builds-up a picture of the event. The input to the Pandora pattern recognition is a list of 2D Hits. The output from the chain of over 70 algorithms is a hierarchy of reconstructed 3D Particles, each with an identified particle type, vertex and direction

Leukotriene B4 (LTB4) and its receptor in Experimental Autoimmune Uveitis (EAU) and in human retinal tissues: clinical severity and LTB4-dependence of retinal Th17 cells

Nomacopan, a drug originally derived from tick saliva, has dual functions of sequestering leukotriene B4 (LTB4) and inhibiting complement component 5 (C5) activation. It was demonstrated that nomacopan provides therapeutic benefit in experimental autoimmune uveitis (EAU). The longer-acting forms of nomacopan were more efficacious in mouse EAU models and the long-acting variant that inhibited only LTB4 was at least as effective as the long-acting variant that inhibited both C5 and LTB4, preventing structural damage to the retina and a significant reduction of effector Th17 cells and inflammatory macrophages. Increased levels of LTB4 and C5a (produced upon C5 activation) were detected during disease progression. Retinal activated lymphocytes were shown to express LTB4 receptors (R) in vitro and in inflamed draining lymph nodes (dLN). Levels of LTB4R-expressing retinal active/inflammatory macrophages were also increased. Within the dLN CD4+T cell population, 30% expressed LTB4R+ following activation in vitro, while retinal infiltrating cells expressed LTB4R and C5aR. Validation of expression of those receptors in human uveitis and healthy tissues suggests that infiltrating cells could be targeted by inhibitors of the LTB4-BLT1 pathway as a novel therapeutic approach. In conclusion, this study provides novel data on intraocular LTB4 and C5a in EAU, their associated receptor expression by retinal infiltrating cells in mouse and human tissues and in attenuating EAU via the dual inhibitor nomacopan

In search of a working notion of lex sportiva

The emergence of a lex specialis regime and its interaction with the established, governing lex generalis in their overlapping spheres of application is always an intriguing legal relationship to explore. In this article, the focus will be on the development of legal principles and rules that have been/can be collectively described as lex sportiva. However, it is notable that those involved in the consideration, usage and application of this notion have not agreed as to the scope and delimitation of the concept. It is debated whether lex sportiva exists in the first place, its legal sources and its purpose. The risk is for the concept becoming redundant when not vilified as a hidden strategy to exclude non-sports-related law from the ambit of sport. Through an examination of the different propositions to the framework of the term, this article will shed light on the existence, utility and limits of the development of this conceptualisation

Woodland birds and rural towns: artificial clutch survival in fragmented Box-Ironbark forests

Woodland birds are declining throughout the agricultural landscapes of south-eastern Australia, but the specific mechanisms driving these declines remain unclear. Reproductive failure via clutch depredation could conceivably contribute to these declines. Although site-scale habitat may influence the risk of clutch failure, larger-scale influences, such as whether a landscape contains a rural town or not (‘landscape type’), may also play a role. This study monitored artificial open-cup nests deployed in three pairs of the two landscape types and: 1) indexed clutch survival and predator assemblage; and 2) determined if clutch survival was influenced by landscape type and/or local habitat characteristics. High levels of clutch depredation were observed in both landscape types and for all landscapes, with no evidence to suggest that landscape type or habitat characteristics influenced clutch survival or the time-to-first-predator visit. Predator assemblage also was consistent between landscape types. Generalist avian predators were the most common egg predators. Such egg predators may be ubiquitous throughout the fragmented Box-Ironbark woodlands of south-eastern Australia