This article contributes a novel method to assess robot dexterity. Existing Jacobian-based dexterity metrics, such as the manipulability index or the condition number, do not allow for comparisons ...between robot architectures, are local in nature, and are affected by robot dimensions (robot size). On the contrary, the introduced metric is global and allows for quantitative comparisons of robot architectures as it explicitly incorporates the orientational and positional coverage of a robot's end-effector. Experiments presented show that the proposed dexterity metric can improve the computational and precision performance of numerical inverse kinematics and showcase its suitability for use in computational dexterous robot design and, in particular, for designing concentric tube robots with high orientational and positional dexterity.
To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute ...neovascular age-related macular degeneration (AMD).
Prospective interventional cohort study.
Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy.
Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch's membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector.
Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft.
Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation.
Autologous RPE transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.
Optical coherence tomography (OCT) is a commonly used imaging modality that provides detailed cross-sectional retinal images. This has revolutionised management of neovascular age-related macular ...degeneration. The need for repeated anti-vascular endothelial growth factor injections has led to therapy being delivered using OCT-guided retreatment strategies with both qualitative OCT features of disease activity (e.g. macular fluid) and changes in retinal thickness as triggers for retreatment The purpose of this study is to determine the intra-session repeatability of retinal thickness and volume measurements using the Topcon 3DOCT-1000 spectral-domain optical coherence tomography (SDOCT) device in patients with neovascular age-related macular degeneration (nAMD). This is the largest study to date looking specifically at the Topcon 3DOCT-1000.
Two SDOCT raster scans were performed by the same blinded observer in the same sitting in consecutive patients attending for nAMD treatment as part of standard validation of a new device. Retrospective analysis was undertaken, with retinal thickness and volume measurements automatically calculated by the onboard software for each Early Treatment of Diabetic Retinopathy Study subfield for each scan. Bland-Altman methods of analysis were used to assess repeatability.
Data from the 73 patients were analyzed with a mean age of 78 years (standard deviation 8). The 95% coefficient of repeatability (CR) was 64 μm and 0.050 mm 3 for retinal thickness and volume respectively in the central 1 mm macular subfield. The CR did not exceed 85 μm (0.30 mm 3 ) in any subfield. The revised CR for retinal thickness and volume for the subgroup of 37 patients with no segmentation error in the central 1 mm subfield was 53 μm and 0.050 mm 3 respectively. Discussion : We report relatively modest intra-sessional repeatability of SDOCT retinal thickness and volume metrics in patients with nAMD in a clinical setting. Though useful in detecting clinical change from measurement variability in clinical practice, these results suggest the precision of macular thickness measurement does not approach the theoretical resolution of SDOCT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cultured retinal pigment epithelium (RPE) may become a therapeutic option for transplantation in retinal disease. However maintaining a native RPE phenotype in vitro has proven challenging. The human ...RPE cell-line ARPE-19 is used widely as an alternative to primary RPE. It is grown in DMEM/F12 medium as standard, but its phenotype is dependent on culture conditions, and many differentiation markers are usually absent. The purpose of this study was to examine how this sensitive phenotype of ARPE-19 can be modulated by growth media with or without the metabolite pyruvate to elucidate better RPE growth conditions.
ARPE-19 cells at passages p22 to p28 were cultured on filters for up to 3 months in DMEM/F12 or DMEM media with or without pyruvate and 1% fetal calf serum. Assessment of differentiation was performed using pigmentation, immunocytochemistry, protein/mRNA expression, transepithelial resistance, VEGF secretion, and ultrastructure.
Pyruvate, in combination with DMEM, induced dark pigmentation and promoted differentiation markers such as CRALBP and MerTK. Importantly, RPE65 protein was detected by Western blotting and was enhanced by pyruvate, high glucose, and DMEM. ARPE-19 cells maintained in this medium could also phagocytose human photoreceptor outer segments (POS). VEGF secretion was greater in DMEM cultures and was affected by glucose but not by pyruvate. Pigmentation never occurred in DMEM/F12.
This study demonstrated important differentiation markers, including pigmentation and Western blots of RPE65 protein, and showed human POS phagocytosis in ARPE-19 cultures using a simple differentiation protocol. The results favor the use of high-glucose DMEM with pyruvate for future RPE differentiation studies.
The Argus® II Retinal Prosthesis System Luo, Yvonne Hsu-Lin; da Cruz, Lyndon
Progress in retinal and eye research,
January 2016, 2016-Jan, 2016-01-00, 20160101, Letnik:
50
Journal Article
Recenzirano
The Argus® II Retinal Prosthesis System (Second Sight Medical Products) is the first prosthetic vision device to obtain regulatory approval in both Europe and the USA. As such it has entered the ...commercial market as a treatment for patients with profound vision loss from end-stage outer retinal disease, predominantly retinitis pigmentosa. To date, over 100 devices have been implanted worldwide, representing the largest group of patients currently treated with visual prostheses.
The system works by direct stimulation of the relatively preserved inner retina via epiretinal microelectrodes, thereby replacing the function of the degenerated photoreceptors. Visual information from a glasses-mounted video camera is converted to a pixelated image by an external processor, before being transmitted to the microelectrode array at the macula. Elicited retinal responses are then relayed via the normal optic nerve to the cortex for interpretation.
We reviewed the animal and human studies that led to the development of the Argus® II device. A sufficiently robust safety profile was demonstrated in the phase I/II clinical trial of 30 patients. Improvement of function in terms of orientation and mobility, target localisation, shape and object recognition, and reading of letters and short unrehearsed words have also been shown. There remains a wide variability in the functional outcomes amongst the patients and the factors contributing to these performance differences are still unclear. Future developments in terms of both software and hardware aimed at improving visual function have been proposed. Further experience in clinical outcomes is being acquired due to increasing implantation.
Background Choroideremia is an X-linked inherited retinal degeneration that begins in childhood with nyctalopia and loss of peripheral vision, and gradually progresses to blindness in adulthood. ...Choroideremia is caused by null mutations in the CHM gene, which encodes Rab escort protein 1. Objective Assessment of the efficacy and safety of a single subretinal injection of an adeno-associated virus serotype 2 vector encoding Rab escort protein 1 in patients with choroideremia. Design Multicentre open-label clinical trial of a gene therapy for choroideremia using an adeno-associated virus serotype 2-Rab escort protein 1 vector. Setting This study (NCT02407678) was conducted at two NHS eye hospitals in the UK. Participants Males aged 18 years or above, having a clinical diagnosis of choroideremia with genetic confirmation of CHM gene mutation or molecular confirmation of Rab escort protein 1 protein deficiency and having best corrected visual acuity better than or equal to 6/60 (20/200; LogMAR 1.0). Intervention Adeno-associated virus serotype 2-Rab escort protein 1 vector suspension (1 × 10 12 vector particles per ml) was supplied by Nightstar Therapeutics (London, UK), now part of Biogen Inc. (Cambridge, MA, USA). Up to 0.1 ml of adeno-associated virus serotype 2-Rab escort protein 1 vector suspension, corresponding to a dose of up to 1 × 10 11 vector particles, was administered to the treated eye by subretinal injection. Selection of treated eyes was randomised in participants having relatively symmetrical retinal degeneration. Main outcome measures The primary safety-related outcome was change from baseline in best corrected visual acuity in treated eyes at 24 months post treatment, with prospective efficacy evaluated by comparative change from baseline in best corrected visual acuity in treated and untreated contralateral (control) eyes. Secondary outcomes included comparative change from baseline in mean retinal sensitivity (microperimetry) and retinal anatomy (area of autofluorescence) in treated and control eyes. Visual assessments were conducted by masked assessors. Results The primary efficacy-related outcome (comparative change from baseline in best corrected visual acuity in treated and control eyes at 24 months post treatment) was not statistically different between treated eyes (−2.63 letters, standard error of the mean 2.76) and control eyes (+2.67 letters, standard error of the mean 0.768) in all 30 participants ( p = 0.08). Greater loss of visual fields, possibly surgery-induced, was observed in treated eyes. Six serious adverse events were reported in the treated eyes of four participants: one surgery-related and two inflammation-related serious adverse events involving clinically significant decreases in best corrected visual acuity, and three serious adverse events in one participant involving reduction in central retinal sensitivity, but with best corrected visual acuity remaining stable. Limitations No evidence of possible efficacy of the intervention was observed, as a meaningful difference in comparative change from baseline in best corrected visual acuity in treated and control eyes was not discernible at 24 months post treatment. As choroideremia is a very slow degeneration, best corrected visual acuity in control eyes did not decline significantly during the assessment period. Conclusion Although this study has not presented evidence that reduction in visual fields caused by the intervention would be justified by the possible rescue of best corrected visual acuity, a more definitive assessment may be provided by long-term monitoring of trial participants in an observational study (NCT03584165). Trial registration This study is registered as ISRCTN15602229 (www.isrctn.com/) and NCT02407678 (https://clinicaltrials.gov/). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/66/35) and is published in full in Efficacy and Mechanism Evaluation ; Vol. 11, No. 9. See the NIHR Funding and Awards website for further award information.
(1) Background: We reviewed a stem cell-derived therapeutic strategy for advanced neovascular age-related macular degeneration (nAMD) using a human embryonic stem cell-derived retinal pigment ...epithelium (hESC-RPE) monolayer delivered on a coated, synthetic basement membrane (BM)-the patch-and assessed the presence and distribution of hESC-RPE over 5 years following transplantation, as well as functional outcomes. (2) Methods: Two subjects with acute vision loss due to sub-macular haemorrhage in advanced nAMD received the hESC-RPE patch. Systematic immunosuppression was used peri-operatively followed by local depot immunosuppression. The subjects were monitored for five years with observation of RPE patch pigmentation, extension beyond the patch boundary into surrounding retina, thickness of hESC-RPE and synthetic BM and review for migration and proliferation of hESC-RPE. Visual function was also assessed. (3) Results: The two study participants showed clear RPE characteristics of the patch, preservation of some retinal ultrastructure with signs of remodelling, fibrosis and thinning on optical coherence tomography over the 5-year period. For both participants, there was evidence of pigment extension beyond the patch continuing until 12 months post-operatively, which stabilised and was preserved until 5 years post-operatively. Measurement of hESC-RPE and BM thickness over time for both cases were consistent with predefined histological measurements of these two layers. There was no evidence of distant RPE migration or proliferation in either case beyond the monolayer. Sustained visual acuity improvement was apparent for 2 years in both subjects, with one subject maintaining the improvement for 5 years. Both subjects demonstrated initial improvement in fixation and microperimetry compared to baseline, at year 1, although only one maintained this at 4 years post-intervention. (4) Conclusions: hESC-RPE patches show evidence of continued pigmentation, with extension, to cover bare host basement membrane for up to 5 years post-implantation. There is evidence that this represents functional RPE on the patch and at the patch border where host RPE is absent. The measurements for thickness of hESC-RPE and BM suggest persistence of both layers at 5 years. No safety concerns were raised for the hypothetical risk of RPE migration, proliferation or tumour formation. Visual function also showed sustained improvement for 2 years in one subject and 5 years in the other subject.
Reconfigurable parallel mechanisms have legs or end-effectors with additional degrees of freedom or with the ability to change their mobility. This allows them to reconfigure into a variety of ...conventional parallel mechanisms. One type of reconfigurable parallel mechanism can be obtained by replacing the end-effector with a closed-loop linkage. The parts of this linkage that are connected to the legs may be considered as the end-effectors, having their own mobility relative to the base and a coupled mobility with each other. Classical methods for mobility analysis cannot be directly applied to this type of mechanism. This article presents a general method to calculate and represent the coupled mobility of the multiple end-effectors using nullspace operations on a matrix of mobility. The nullspace approach provides an efficient way to calculate the mobility in a closed-loop chain while the matrix of mobility allows for calculating the multiple end-effectors mobility interaction. The general method can be performed analytically to obtain insights on the mechanism in any configuration, or algorithmically to obtain numerical values of the mobility in a particular configuration. Two illustrative examples showcasing the method are presented.
•Limitations in the mobility analysis of general parallel mechanisms are presented.•The nullspace approach is extended to the mobilities of a single closed-loop.•A matrix of mobility combining all mobilities into one vector space is presented.•The nullspace approach and the matrix of mobility are combined to form the method.•Two examples showcasing the method analytically and algorithmically are presented.
We present oflibnumpy and oflibpytorch, an optical flow library based on NumPy arrays and PyTorch tensors, respectively. It provides a structured approach to the representation of optical flow, i.e ...2D vector fields, as a custom class offering a number of methods to apply, manipulate, analyse, and visualise the flow. The library takes into account the two possible frames of reference in optical flow calculation, namely the source (first frame) and target (second frame). The collection of methods and their rigorous mathematical underpinning makes the library broadly applicable to any project that uses flow fields. It is implemented as a Python 3 package whose source can be found on GitHub, and which can be installed either from the git repository or the Python Package Index (PyPI). Keywords: Optical flow, Flow field, Flow vector, Flow composition, Python, NumPy, PyTorch
Soft robot's natural dynamics calls for the development of tailored modeling techniques for control. However, the high-dimensional configuration space of the geometrically exact modeling approaches ...for soft robots, i.e., Cosserat rod and Finite Element Methods (FEM), has been identified as a key obstacle in controller design. To address this challenge, Reduced Order Modeling (ROM), i.e., the approximation of the full-order models, and Model Order Reduction (MOR), i.e., reducing the state space dimension of a high fidelity FEM-based model, are enjoying extensive research. Although both techniques serve a similar purpose and their terms have been used interchangeably in the literature, they are different in their assumptions and implementation. This review paper provides the first in-depth survey of ROM and MOR techniques in the continuum and soft robotics landscape to aid Soft Robotics researchers in selecting computationally efficient models for their specific tasks.
PDF
