Evaluation of Microcollimated Pars Plana External Beam Radiation in the Porcine Eye

Purpose: To evaluate the clinical and histological side effects of a prototype stereotactic radiotherapy system delivering microcollimated external beam radiation through pars plana in porcine eyes.

Methods: Five Yucatan mini-swine (10 eyes) were randomized to five treatment groups. Eight eyes were dosed with X-ray radiation on Day 1, and two eyes served as untreated controls. Treated eyes received doses up to 60 Gy to the retina and up to 130 Gy to the sclera using single or overlapping beams. The treatment beams were highly collimated such that the diameter was approximately 2.5 mm on the sclera and 3 mm on the retinal surface. Fundus photography, fluorescein angiography (FA), and spectral domain optical coherence tomography (SD-OCT) were obtained on days 7, 30, 60, and 110. Images were examined by a masked grader and evaluated for abnormalities. Animals were sacrificed on day 111 and gross and histopathological analysis was conducted.

Results: Histological and gross changes to eye structures including conjunctiva and lens were minimal at all doses. Fundus, FA, and SD-OCT of the targeted region failed to disclose any abnormality in the control or 21 Gy treated animals. In the 42 and 60 Gy animals, hypopigmented spots were noted after treatment on clinical exam, and corresponding hyperfluorescent staining was seen in late frames. No evidence of choroidal hypoperfusion was seen. The histological specimens from the 60 Gy animals showed photoreceptor loss and displacement of cone nuclei.

Conclusion: Transcleral stereotactic radiation dosing in porcine eyes can be accomplished with no significant adverse events as doses less than 42 Gy.

Behavioural context of multi-scale species distribution models assessed by radio-tracking

Incorporating ecological processes and animal behaviour into Species Distribution Models (SDMs) is difficult. In species with a central resting or breeding place, there can be conflict between the environmental requirements of the 'central place' and foraging habitat. We apply a multi-scale SDM to examine habitat trade-offs between the central place, roost sites, and foraging habitat in . Myotis nattereri. We validate these derived associations using habitat selection from behavioural observations of radio-tracked bats. A Generalised Linear Model (GLM) of roost occurrence using land cover variables with mixed spatial scales indicated roost occurrence was positively associated with woodland on a fine scale and pasture on a broad scale. Habitat selection of radio-tracked bats mirrored the SDM with bats selecting for woodland in the immediate vicinity of individual roosts but avoiding this habitat in foraging areas, whilst pasture was significantly positively selected for in foraging areas. Using habitat selection derived from radio-tracking enables a multi-scale SDM to be interpreted in a behavioural context. We suggest that the multi-scale SDM of . M. nattereri describes a trade-off between the central place and foraging habitat. Multi-scale methods provide a greater understanding of the ecological processes which determine where species occur and allow integration of behavioural processes into SDMs. The findings have implications when assessing the resource use of a species at a single point in time. Doing so could lead to misinterpretation of habitat requirements as these can change within a short time period depending on specific behaviour, particularly if detectability changes depending on behaviour. © 2011 Gesellschaft für ökologie.

Newly Acquired Fear of Falling Leads to Altered Eye Movement Patterns and Reduced Stepping Safety: A Case Study

This opportune case study describes visual and stepping behaviours of an 87 year old female (P8), both prior to, and following two falls. Before falling, when asked to walk along a path containing two stepping guides positioned before and after an obstacle, P8 generally visually fixated the first stepping guide until after foot contact inside it. However, after falling P8 consistently looked away from the stepping guide before completing the step into it in order to fixate the upcoming obstacle in her path. The timing of gaze redirection away from the target (in relation to foot contact inside it) correlated with absolute stepping error. No differences in eyesight, cognitive function, or balance were found between pre- and post-fall recordings. However, P8 did report large increases in fall-related anxiety and reduced balance confidence, supporting previously suggested links between anxiety/increased fear or falling and maladaptive visual/stepping behaviours. The results represent a novel insight into how psychological and related behavioural factors can change in older adults following a fall, and provide a possible partial rationalisation for why recent fallers are more likely to fall again in the following 12 months. These findings highlight novel possibilities for falls prevention and rehabilitation.

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms:a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

Analysis of Dependence Tracking Algorithms for Task Dataflow Execution

Processor architectures has taken a turn towards many-core processors, which integrate multiple processing cores on a single chip to increase overall performance, and there are no signs that this trend will stop in the near future. Many-core processors are harder to program than multi-core and single-core processors due to the need of writing parallel or concurrent programs with high degrees of parallelism. Moreover, many-cores have to operate in a mode of strong scaling because of memory bandwidth constraints. In strong scaling increasingly finer-grain parallelism must be extracted in order to keep all processing cores busy.

Task dataflow programming models have a high potential to simplify parallel program- ming because they alleviate the programmer from identifying precisely all inter-task de- pendences when writing programs. Instead, the task dataflow runtime system detects and enforces inter-task dependences during execution based on the description of memory each task accesses. The runtime constructs a task dataflow graph that captures all tasks and their dependences. Tasks are scheduled to execute in parallel taking into account dependences specified in the task graph.

Several papers report important overheads for task dataflow systems, which severely limits the scalability and usability of such systems. In this paper we study efficient schemes to manage task graphs and analyze their scalability. We assume a programming model that supports input, output and in/out annotations on task arguments, as well as commutative in/out and reductions. We analyze the structure of task graphs and identify versions and generations as key concepts for efficient management of task graphs. Then, we present three schemes to manage task graphs building on graph representations, hypergraphs and lists. We also consider a fourth edge-less scheme that synchronizes tasks using integers. Analysis using micro-benchmarks shows that the graph representation is not always scalable and that the edge-less scheme introduces least overhead in nearly all situations.

Generalized Laplacian Eigenmaps for Modeling and Tracking Human Motions

This paper presents generalized Laplacian eigenmaps, a novel dimensionality reduction approach designed to address stylistic variations in time series. It generates compact and coherent continuous spaces whose geometry is data-driven. This paper also introduces graph-based particle filter, a novel methodology conceived for efficient tracking in low dimensional space derived from a spectral dimensionality reduction method. Its strengths are a propagation scheme, which facilitates the prediction in time and style, and a noise model coherent with the manifold, which prevents divergence, and increases robustness. Experiments show that a combination of both techniques achieves state-of-the-art performance for human pose tracking in underconstrained scenarios.

Tracking down the cause of proteinuria in primary care

Proteinuria originates from the kidney and occurs as a result of injury to either the glomerulus or the renal tubule or both. It is relatively common in the general population with reported point prevalence of up to 8% but the prevalence falls to around 2% on repeated testing. Chronic glomerular injury resulting in proteinuria may be secondary to prolonged duration of diabetes or hypertension. A tubular origin of proteinuria may be associated with inflammation of renal tubules triggered by prescribed drugs or ingested toxins. In the absence of obvious clues to the cause of persistent proteinuria on history or clinical examination it is worthwhile reviewing the patient's prescribed drugs to identify any potentially nephrotoxic agents e.g. NSAIDs. NICE guidelines recommend screening for proteinuria in individuals at higher risk for chronic kidney disease (CKD). These include patients with diabetes, hypertension, cardiovascular disease, connective tissue disorders, a family history of renal disease and those prescribed potentially nephrotoxic drugs. Patients with sudden onset of lower limb oedema and associated proteinuria should have a serum albumin level measured to exclude the nephrotic syndrome. Renal tract ultrasound will measure kidney size, and detect scarring associated with chronic pyelonephritis or prior renal stone disease which can cause proteinuria.

Will VEGF Trap-Eye reduce the treatment burden in neovascular age-related macular degeneration?

Evaluation of: Brown DM, Heier JS, Ciulla T et al. Primary end point results of a Phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology 118(6), 1089-1097 (2011); Heier JS, Boyer D, Nguyen QD et al. The 1-year results of CLEAR-IT 2, a Phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing. Ophthalmology 118(6), 1098-1106 (2011). Age-related macular degeneration is the most common cause of blindness in older adults in western countries, and is likely to become the largest cause of irreversible sight loss in the developing world. Treatments such as ranibizumab and bevacizumab that inhibit VEGF have improved visual outcomes markedly. Controlled trials and clinical experience have shown that the best outcomes are achieved when monthly treatment has been administered over 2 years. This poses a significant burden on health providers and patients. A novel inhibitor of VEGF, VEGF Trap-Eye, which allows less frequent dosing without loss of efficacy, has emerged as a potential treatment. CLEAR-IT 2 was a prospective randomized Phase II trial designed to assess the safety, tolerability and the anatomic and visual effects of repeated treatments with a range of doses of VEGF Trap-Eye. Impressive anatomic and visual improvements were noted with no safety concerns. © 2011 Expert Reviews Ltd.

Adaptive Fusion Of Particle Filtering And Spatio-Temporal Motion Energy For Human Tracking

Object tracking is an active research area nowadays due to its importance in human computer interface, teleconferencing and video surveillance. However, reliable tracking of objects in the presence of occlusions, pose and illumination changes is still a challenging topic. In this paper, we introduce a novel tracking approach that fuses two cues namely colour and spatio-temporal motion energy within a particle filter based framework. We conduct a measure of coherent motion over two image frames, which reveals the spatio-temporal dynamics of the target. At the same time, the importance of both colour and motion energy cues is determined in the stage of reliability evaluation. This determination helps maintain the performance of the tracking system against abrupt appearance changes. Experimental results demonstrate that the proposed method outperforms the other state of the art techniques in the used test datasets.

Clinical Characteristics of Reticular Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration

Purpose: To describe associations between reticular pseudodrusen, individual characteristics, and retinal function.

Design: Cohort study.

Participants: We recruited 105 patients (age range, 52–93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe.

Methods: Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts.

Main Outcome Measures: Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume.

Results: Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1–28.8; P = 0.042). All participants in whom geographic atrophy developed during follow-up had visible RPD at baseline.

Conclusions: Significant differences in retinal and choroidal anatomic features, visual function, and risk factor profile exist in unilateral neovascular AMD patients with RPD compared with those without; therefore, such patients should be monitored carefully because of the risk of developing bilateral disease.

Tracking magnetic bright point motions through the solar atmosphere

High-cadence, multiwavelength observations and simulations are employed for the analysis of solar photospheric magnetic bright points (MBPs) in the quiet Sun. The observations were obtained with the Rapid Oscillations in the Solar Atmosphere (ROSA) imager and the Interferometric Bidimensional Spectrometer at the Dunn Solar Telescope. Our analysis reveals that photospheric MBPs have an average transverse velocity of approximately 1 km s-1, whereas their chromospheric counterparts have a slightly higher average velocity of 1.4 km s-1. Additionally, chromospheric MBPs were found to be around 63 per cent larger than the equivalent photospheric MBPs. These velocity values were compared with the output of numerical simulations generated using the muram code. The simulated results were similar, but slightly elevated, when compared to the observed data. An average velocity of 1.3 km s-1 was found in the simulated G-band images and an average of 1.8 km s-1 seen in the velocity domain at a height of 500 km above the continuum formation layer. Delays in the change of velocities were also analysed. Average delays of ˜4 s between layers of the simulated data set were established and values of ˜29 s observed between G-band and Ca ii K ROSA observations. The delays in the simulations are likely to be the result of oblique granular shock waves, whereas those found in the observations are possibly the result of a semi-rigid flux tube.

Dense Multiperson Tracking with Robust Hierarchical Linear Assignment

We introduce a novel dual-stage algorithm for online multi-target tracking in realistic conditions. In the first stage, the problem of data association between tracklets and detections, given partial occlusion, is addressed using a novel occlusion robust appearance similarity method. This is used to robustly link tracklets with detections without requiring explicit knowledge of the occluded regions. In the second stage, tracklets are linked using a novel method of constraining the linking process that removes the need for ad-hoc tracklet linking rules. In this method, links between tracklets are permitted based on their agreement with optical flow evidence. Tests of this new tracking system have been performed using several public datasets.