Performance Analysis of Cone Detection Algorithms

Many algorithms have been proposed to help clinicians evaluate cone density and spacing, as these may be related to the onset of retinal diseases. However, there has been no rigorous comparison of the performance of these algorithms. In addition, the performance of such algorithms is typically determined by comparison with human observers. Here we propose a technique to simulate realistic images of the cone mosaic. We use the simulated images to test the performance of two popular cone detection algorithms and we introduce an algorithm which is used by astronomers to detect stars in astronomical images. We use Free Response Operating Characteristic (FROC) curves to evaluate and compare the performance of the three algorithms. This allows us to optimize the performance of each algorithm. We observe that performance is significantly enhanced by up-sampling the images. We investigate the effect of noise and image quality on cone mosaic parameters estimated using the different algorithms, finding that the estimated regularity is the most sensitive parameter. This paper was published in JOSA A and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/abstract.cfm?msid=224577. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.Comment: 13 pages, 7 figures, 2 table

GABAergic interneuron communication to astrocytes: a novel modulatory signalling in brain networks

Deciphering the rules governing synaptic communication among neurons is believed to provide the key to understanding how the brain works. Accumulating evidence supports, however, the novel view that the brain should not be regarded simply as a circuit of actively interacting neurons but rather as a network of neurons and astrocytes that intesively cooperate to perform computational feats. Astrocytes respond to the synaptic release of neurotransmitters with intracellular Ca2+ elevations mediated mainly by G-protein coupled receptors, and with the release of neuroactive molecules, collectively termed gliotransmitters, that contribute to the modulation of synaptic transmission and plasticity. The role of neuron-astrocyte interactions has been, however, intensively studied in relation to glutamatergic synaptic transmission, but little has been revealed about the role of astrocytes in GABAergic inhibitory transmission. Indeed, whether the different GABAergic interneurons specifically signal to astrocytes and what impact on the activity of local neuronal circuits this signalling pathway may are fundamental questions that have been poorly addressed. In my thesis I started to investigate the signaling between different interneurons and astrocytes, focusing on Parvalbumin (PV)- and Somatostatin (SOM)-expressing interneuron subpopulations that compose up to 70 % of the total number of GABAergic interneurons in the brain. To this aim, I developed a complex approach that combines single and two-photon laser-scanning microscopy for Ca2+ imaging, both in somatosensory cortex (SSCx) slices and in vivo, patch-clamp recording and optogenetic techniques. I found that in somatosensory and temporal cortex slices loaded with the Ca2+ indicator Fluo-4 AM and the astrocytic marker SR101, about 60 % of layer V astrocytes showed large amplitude somatic Ca2+ increases in response to GABA or baclofen (Bac, a GABAB receptor agonist) in both young and adult mice. These Ca2+ responses were abolished in mice lacking the inositol-1,4,5-trisphosphate (IP3) receptor type 2 in astrocytes, while blocking Gi/o proteins with pertussis toxin prevented Bac-mediated Ca2+ transients. These results reveal an involvement of the Gq/IP3 cascade and suggest possible Gi/o-Gq protein interactions in the astrocyte response to GABA signals. In a mouse model in which astrocytes selectively express the genetically encoded Ca2+ indicator GCaMP3, I also found that local GABA or Bac applications induced long-lasting Ca2+ oscillations at fine processes that occasionally spread to the entire astrocytic soma and other processes. I then validated the responsiveness of astrocytes to GABAergic signals in in vivo experiments from P30-60 anesthetized GCaMP3 animals where Bac locally applied to primary SSCx layers I/II evoked Ca2+ elevations in 45.46 % ± 8.07 % of the total astrocytes observed. Optogenetic stimulation of ChR2-expressing PV or SOM interneurons also evoked astrocytes Ca2+ events (the average of Ca2+ peaks per minute significantly increase from 0.15 ± 0.06 to 0.30 ± 0.05 for PV interneurons stimulation and from 0.19 ± 0.04 to 1.16 ± 0.13 for SOM interneurons stimulation). Current pulse depolarization of a single PV or SOM interneuron increased Ca2+ peaks in nearby astrocytes from 0.41 ± 0.04 to 0.65 ± 0.08 (p<0.05) and event frequency per minute from 0.10 ± 0.31 to 1.09 ± 0.16 (p<0.01), respectively. Patch-clamp recordings in the presence of TTX showed that GABAB activation triggered glutamate release in astrocytes and NMDAR-mediated slow inward currents (SICs) in nearby neurons. The frequency of SICs was strongly increased both in PV interneurons (from 0.15 ± 0.06 to 0.46 ± 0.04 event/min) and pyramidal neurons (from 0.30 ± 0.07 to 0.79 ± 0.17 event/min). The increase in SICs frequency lasted for about two minutes on average, outlasting the time of GABA agonist applications. As revealed in experiments from IP3R2 KO mice, GABA-induced SICs were also dependent on IP3R mediated intracellular Ca2+ transients in astrocytes. These data suggest that astrocytes activated by GABAergic interneurons convert a transient inhibition into a delayed excitation in local circuits. I conclude that cortical astrocytes can be activated by two of the major GABAergic interneuron classes in the brain (PV and SOM). The consequent gliotransmitter release provides a new form of homeostatic control of local network excitability

New Tools to Study Astrocyte Ca2+ Signal Dynamics in Brain Networks In Vivo

Sensory information processing is a fundamental operation in the brain that is based on dynamic interactions between different neuronal populations. Astrocytes, a type of glial cells, have been proposed to represent active elements of brain microcircuits that, through dynamic interactions with neurons, provide a modulatory control of neuronal network activity. Specifically, astrocytes in different brain regions have been described to respond to neuronal signals with intracellular Ca2+ elevations that represent a key step in the functional recruitment of astrocytes to specific brain circuits. Accumulating evidence shows that Ca2+ elevations regulate the release of gliotransmitters that, in turn, modulate synaptic transmission and neuronal excitability. Recent studies also provided new insights into the spatial and temporal features of astrocytic Ca2+ elevations revealing a surprising complexity of Ca2+ signal dynamics in astrocytes. Here we discuss how recently developed experimental tools such as the genetically encoded Ca2+ indicators (GECI), optogenetics and chemogenetics can be applied to the study of astrocytic Ca2+ signals in the living brain

FisheyeMODNet: Moving Object Detection on Surround-view Cameras for Autonomous Driving

Moving Object Detection (MOD) is an important task for achieving robust autonomous driving. An autonomous vehicle has to estimate collision risk with other interacting objects in the environment and calculate an optional trajectory. Collision risk is typically higher for moving objects than static ones due to the need to estimate the future states and poses of the objects for decision making. This is particularly important for near-range objects around the vehicle which are typically detected by a fisheye surroundview system that captures a 360± view of the scene. In this work, we propose a CNN architecture for moving object detection using fisheye images that were captured in autonomous driving environment. As motion geometry is highly non-linear and unique for fisheye cameras, we will make an improved version of the current dataset public to encourage further research. To target embedded deployment, we design a lightweight encoder sharing weights across sequential images. The proposed network runs at 15 fps using Jetston Nvidia TX2 embedded GPU at accuracy of 40% IoU and 69.5% mIoU

Non-neural phenotype of spinal and bulbar muscular atrophy: Results from a large cohort of Italian patients

Objective: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). Methods: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. Results: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. Conclusions: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients. \ua9 2016 Published by the BMJ Publishing Group Limited

mCerulean3-Based Cameleon Sensor to Explore Mitochondrial Ca2+ Dynamics In Vivo

Genetically Encoded Ca2+ Indicators (GECIs) are extensively used to study organelle Ca2+ homeostasis, although some available probes are still plagued by a number of problems, e.g., low fluorescence intensity, partial mistargeting, and pH sensitivity. Furthermore, in the most commonly used mitochondrial F\uf6rster Resonance Energy Transfer based-GECIs, the donor protein ECFP is characterized by a double exponential lifetime that complicates the fluorescence lifetime analysis. We have modified the cytosolic and mitochondria-targeted Cameleon GECIs by (1) substituting the donor ECFP with mCerulean3, a brighter and more stable fluorescent protein with a single exponential lifetime; (2) extensively modifying the constructs to improve targeting efficiency and fluorescence changes caused by Ca2+ binding; and (3) inserting the cDNAs into adeno-associated viral vectors for in vivo expression. The probes have been thoroughly characterized in situ by fluorescence microscopy and Fluorescence Lifetime Imaging Microscopy, and examples of their ex vivo and in vivo applications are described

Acromegaly is associated with increased cancer risk: A survey in Italy

It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 \uc2\ub1 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18-1.68, P &lt; 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07-2.58, P = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55-5.34, P &lt; 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32-6.87, P &lt; 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI