The Argus II Retinal Prosthesis System

The field of retinal prosthetics has seen significant advances in the past 3 decades. Encouraging results from different groups have shown coarse objective functional improvement, using a range of technological and surgical approaches. The Argus II retinal prosthesis system was the first of its kind to receive regulatory approval for commercial use in Europe and the USA. The device is designed to replicate the function of photoreceptors in converting visual information into electrical neural signals in patients with profound visual loss secondary to degenerative retinal disease. Results from a phase II study of 30 patients have demonstrated improved performance in basic tests of visual function, object recognition, letter reading, prehension, orientation and mobility tasks. It is now the most widely implanted retinal prosthetic device worldwide. This chapter provides an overview of the requirements of a retinal prosthetic system, the results from the Argus II device to date, and an insight into some of the challenges and future directions of visually restorative therapies

Disrupted Modularity and Local Connectivity of Brain Functional Networks in Childhood-Onset Schizophrenia

Modularity is a fundamental concept in systems neuroscience, referring to the formation of local cliques or modules of densely intra-connected nodes that are sparsely inter-connected with nodes in other modules. Topological modularity of brain functional networks can quantify theoretically anticipated abnormality of brain network community structure – so-called dysmodularity – in developmental disorders such as childhood-onset schizophrenia (COS). We used graph theory to investigate topology of networks derived from resting-state fMRI data on 13 COS patients and 19 healthy volunteers. We measured functional connectivity between each pair of 100 regional nodes, focusing on wavelet correlation in the frequency interval 0.05–0.1 Hz, then applied global and local thresholding rules to construct graphs from each individual association matrix over the full range of possible connection densities. We show how local thresholding based on the minimum spanning tree facilitates group comparisons of networks by forcing the connectedness of sparse graphs. Threshold-dependent graph theoretical results are compatible with the results of a k-means unsupervised learning algorithm and a multi-resolution (spin glass) approach to modularity, both of which also find community structure but do not require thresholding of the association matrix. In general modularity of brain functional networks was significantly reduced in COS, due to a relatively reduced density of intra-modular connections between neighboring regions. Other network measures of local organization such as clustering were also decreased, while complementary measures of global efficiency and robustness were increased, in the COS group. The group differences in complex network properties were mirrored by differences in simpler statistical properties of the data, such as the variability of the global time series and the internal homogeneity of the time series within anatomical regions of interest

Surgical biomicroscopy-guided intra-operative optical coherence tomography (iOCT) image super-resolution

Purpose: Intra-retinal delivery of novel sight-restoring therapies will require the precision of robotic systems accompanied by excellent visualisation of retinal layers. Intra-operative Optical Coherence Tomography (iOCT) provides cross-sectional retinal images in real time but at the cost of image quality that is insufficient for intra-retinal therapy delivery.This paper proposes a super-resolution methodology that improves iOCT image quality leveraging spatiotemporal consistency of incoming iOCT video streams. Methods: To overcome the absence of ground truth high-resolution (HR) images, we first generate HR iOCT images by fusing spatially aligned iOCT video frames. Then, we automatically assess the quality of the HR images on key retinal layers using a deep semantic segmentation model. Finally, we use image-to-image translation models (Pix2Pix and CycleGAN) to enhance the quality of LR images via quality transfer from the estimated HR domain. Results: Our proposed methodology generates iOCT images of improved quality according to both full-reference and no-reference metrics. A qualitative study with expert clinicians also confirms the improvement in the delineation of pertinent layers and in the reduction of artefacts. Furthermore, our approach outperforms conventional denoising filters and the learning-based state-of-the-art. Conclusions: The results indicate that the learning-based methods using the estimated, through our pipeline, HR domain can be used to enhance the iOCT image quality. Therefore, the proposed method can computationally augment the capabilities of iOCT imaging helping this modality support the vitreoretinal surgical interventions of the future

IMAPS Observations of Interstellar Neutral Argon and the Implications for Partially Ionized Gas

We use the absorption features from neutral argon at 1048 and 1066 A to determine interstellar abundances or their lower limits toward nine early-type stars. These features were observed with the Interstellar Medium Absorption Profile Spectrograph (IMAPS) along sight lines with low reddening and low fractional abundances of molecular hydrogen. We find that the interstellar Ar I is below its solar and B-star abundance with respect to hydrogen toward zeta Pup, gamma2 Vel and beta Cen A with (logarithmic) reduction factors -0.37+/-0.09, -0.18+/-0.10, and -0.61+/-0.12 dex, respectively. While Ar can condense onto the surfaces of dust grains in the interiors of dense clouds, it is unlikely that argon atoms are depleted by this process in the low-density lines of sight considered in this study. Instead, we propose that the relatively large photoionization cross section of Ar makes it much easier to hide in its ionized form than H. In regions that are about half ionized, this effect can lower Ar I/H I by -0.11 to -0.96 dex, depending on the energy of the photoionizing radiation and its intensity divided by the local electron density. We apply this interpretation for the condition of the gas in front of beta Cen A, which shows the largest deficiency of Ar. Also, we determine the expected magnitudes of the differential ionizations for He, N, O, Ne and Ar in the partly ionized, warm gas in the local cloud around our solar system. For the local cloud and others that can be probed by UV studies, the observed Ar I to H I ratio may be a good discriminant between two possible alternatives, collisional ionization or photoionization, for explaining the existence of partly ionized regions.Comment: 36 pages, 3 figure

DNA Damage Measured by the Comet Assay in Head and Neck Cancer Patients Treated with Tirapazamine

AbstractTirapazamine (TPZ) [3-amino -1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone™] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZinduced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers

Gene expression differences in relation to age and social environment in queen and worker bumble bees

Eusocial insects provide special insights into the genetic pathways influencing aging because of their long-lived queens and flexible aging schedules. Using qRT-PCR in the primitively eusocial bumble bee Bombus terrestris (Linnaeus), we investigated expression levels of four candidate genes associated with taxonomically widespread age-related pathways (coenzyme Q biosynthesis protein 7, COQ7; DNA methyltransferase 3, Dnmt3; foraging, for; and vitellogenin, vg). In Experiment 1, we tested how expression changes with queen relative age and productivity. We found a significant age-related increase in COQ7 expression in queen ovary. In brain, all four genes showed higher expression with increasing female (queen plus worker) production, with this relationship strengthening as queen age increased, suggesting a link with the positive association of fecundity and longevity found in eusocial insect queens. In Experiment 2, we tested effects of relative age and social environment (worker removal) in foundress queens and effects of age and reproductive status in workers. In this experiment, workerless queens showed significantly higher for expression in brain, as predicted if downregulation of for is associated with the cessation of foraging by foundress queens following worker emergence. Workers showed a significant age-related increase in Dnmt3 expression in fat body, suggesting a novel association between aging and methylation in B. terrestris. Ovary activation was associated with significantly higher vg expression in fat body and, in younger workers, in brain, consistent with vitellogenin's ancestral role in regulating egg production. Overall, our findings reveal a mixture of novel and conserved features in age-related genetic pathways under primitive eusociality