114 results on '"Gabriela Czanner"'
Search Results
2. Amniotic membrane application in surgical treatment of conjunctival tumors
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Alena Furdova, Gabriela Czanner, Jan Koller, Pavol Vesely, Robert Furda, and Zuzana Pridavkova
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Medicine ,Science - Abstract
Abstract The amniotic membrane (AM) has special properties, making it ideal for clinical applications in various surgical fields like ophthalmology. It is used more frequently to cover conjunctival and corneal defects. In our retrospective study we have been combined 68 patients with epibulbar conjunctival tumors they have been surgically treated in the period of 2011–2021. Seven (10.3%) patients have been treated with AM application after surgical removal of the tumor. 54 (79%) cases were malignant, and 14 (21%) were benign. In the analyzed dataset the males had just slightly higher chance of malignancy than females, 80% versus 78.3%. For the significancy calculation the Fisher exact test was used and the result proved no significancy (p = 0.99). Six patients with AM application were malignant. The observed difference in the number of quadrants of the bulbar conjunctiva infiltrated versus significant malignancy with p = 0.050 calculated by Fisher Exact test and with p = 0.023 calculated by Likelihood-ratio test. The results of our study indicate that AM grafts are an effective alternative to cover defects after removal of epibulbar lesions due to their anti-inflammatory properties because the conjunctiva must be preserved, and especially the most important application is in malignant epibulbar conjunctival tumors.
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- 2023
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3. OP-1 Analysis and reporting of surgically induced keratometric effect (SIKE)
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Vito Romano, Stephen Kaye, Gabriela Czanner, Luca Pagano, Esmaeil M Arbabi, Fadi Alfaqawi, and Ahmed Al-Maskari
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Ophthalmology ,RE1-994 - Published
- 2023
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4. The management of anticoagulants in patients with atrial fibrillation and history of falls or risk of falls: protocol for a systematic review and meta-analysis
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Thibaut Galvain, Ruaraidh Hill, Sarah Donegan, Paulo Lisboa, Gregory Y. H. Lip, and Gabriela Czanner
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Systematic review ,Meta-analysis ,VKA ,NOAC ,Falls ,Atrial fibrillation ,Medicine - Abstract
Abstract Background Atrial fibrillation affects an estimated 33 million individuals worldwide and is a major cause of stroke, heart failure, and death. Anticoagulants substantially reduce the risk of stroke but are also associated with an increased risk of bleeding and especially intracranial hemorrhage which is the most concerning complication. Because of this, many patients are not offered anticoagulants, particularly patients at risk of falls or with a history of falls. It is unclear what anticoagulant treatment these patients should be offered. The Liverpool AF-Falls project aims to investigate this area, and this protocol for a systematic review and meta-analysis aims to define what is the most appropriate anticoagulant treatment option for the management of atrial fibrillation patients at risk of falls or with a history of falls. Methods This systematic review and meta-analysis will include randomized and non-randomized studies evaluating the safety and efficacy of different anticoagulant treatments (vitamin K antagonist and non-vitamin K antagonist oral anti-coagulant). Bibliographic databases (Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov , Embase, MEDLINE, Scopus and Web of Science) will be searched according to a pre-specified search strategy. Titles, abstracts, and full texts will be assessed by two independent reviewers and disagreements resolved with a third independent reviewer. The Cochrane Risk of Bias tool 2 (RoB 2) will be used to assess the risk of bias in randomized trials, and the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool will be used for non-randomized studies. A pairwise meta-analysis based on the fixed and random-effects models will be conducted. Publication bias will be evaluated with a funnel plot and Egger’s test. Heterogeneity will be assessed with the I 2 statistic. If conditions for indirect comparison are met and sufficient data are available, a network meta-analysis will be conducted using frequentist and Bayesian methodologies. Discussion This review will be the first to summarize direct and indirect evidence on the safety and efficacy of anticoagulant treatments in atrial fibrillation patients at risk of falls or with a history of falls. The findings will be important to patients, clinicians, and health policy-makers to inform best practices in the use of these treatments. Systematic review registration PROSPERO registry number: CRD42020201086
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- 2022
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5. Visual risk factors for falls in older adults: a case-control study
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Jignasa Mehta, Gabriela Czanner, Simon Harding, David Newsham, and Jude Robinson
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Falls ,Vision ,Depth perception ,Contrast sensitivity ,Social determinants ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background Falls are the second leading cause of accidental deaths worldwide mainly in older people. Older people have poor vision and published evidence suggests that it is a risk factor for falls. Less than half of falls clinics assess vision as part of the multi-factorial assessment of older adults at risk of falls despite vision being an essential input for postural stability. The aim of our study was to investigate the relationship between all clinically assessed visual functions and falls amongst older adults in a prospective observational individually age-matched case control study. Methods Visual acuity (VA), contrast sensitivity (CS), depth perception, binocular vision and binocular visual field were measured using routinely used clinical methods in falls participants (N = 83) and non-falls participants (N = 83). Data were also collected on socio-demographic factors, general health, number of medications, health quality, fear of falling and physical activity. Logistic regression analysis was carried out to determine key visual and non-visual risk factors for falls whilst adjusting for confounding covariates. Results Older adults have an increased risk of experiencing a fall if they have reduced visual function (odds ratio (OR): 3.49, 1.64-7.45, p = 0.001), specifically impaired stereoacuity worse than 85” of arc (OR: 3.4, 1.20-9.69, p = 0.02) and reduced (by 0.15 log unit) high spatial frequency CS (18 cpd) (OR:1.40, 1.12-1.80, p = 0.003). Older adults with a hearing impairment are also at higher risk of falls (OR: 3.18, 95% CI: 1.36-7.40, p = 0.007). The risk decreases with living in a less deprived area (OR: 0.74, 0.64-0.86,
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- 2022
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6. Potential new fluoroquinolone treatments for suspected bacterial keratitis
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Timothy Neal, Stephen B Kaye, Stephen Tuft, Tobi Somerville, Gabriela Czanner, Keri McLean, Rose Herbert, Mary Caddick, and Shakeel Herwitker
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Ophthalmology ,RE1-994 - Abstract
Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use. For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae and several of the Enterobacteriaceae. However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. The purpose of this review is to compare the pharmacokinetics and pharmacodynamics of the FQs licensed for topical ophthalmic use with the same parameters for new generation FQs. We performed a literature review of the FQs approved for topical treatment and the new generation FQs licensed to treat systemic infections. We then compared the minimum inhibitory concentrations (MIC) of bacterial isolates and the published concentrations that FQs achieved in the cornea and aqueous. We also considered the potential suitability of new generation FQs for topical use based on their medicinal properties. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to continue with the prescribed antimicrobial, increase the frequency of application, use a combination of antimicrobials or change treatment.
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- 2022
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7. Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice
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Katie J. Lee, Lisa Rambault, George Bou-Gharios, Peter D. Clegg, Riaz Akhtar, Gabriela Czanner, Rob van ‘t Hof, and Elizabeth G. Canty-Laird
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collagen ,homotrimer ,col1a2 ,α2(i) ,osteogenesis imperfecta ,cveds ,Medicine ,Pathology ,RB1-214 - Published
- 2022
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8. Murine models of renal ischemia reperfusion injury: An opportunity for refinement using noninvasive monitoring methods
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Rachel Harwood, Joshua Bridge, Lorenzo Ressel, Lauren Scarfe, Jack Sharkey, Gabriela Czanner, Philip A Kalra, Aghogho Odudu, Simon Kenny, Bettina Wilm, and Patricia Murray
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acute kidney injury ,chronic kidney disease ,ischemia reperfusion injury ,Physiology ,QP1-981 - Abstract
Abstract Background Renal ischemia reperfusion injury (R‐IRI) can cause acute kidney injury (AKI) and chronic kidney disease (CKD), resulting in significant morbidity and mortality. To understand the underlying mechanisms, reproducible small‐animal models of AKI and CKD are needed. We describe how innovative technologies for measuring kidney function noninvasively in small rodents allow successful refinement of the R‐IRI models, and offer the unique opportunity to monitor longitudinally in individual animals the transition from AKI to CKD. Methods Male BALB/c mice underwent bilateral renal pedicle clamping (AKI) or unilateral renal pedicle clamping with delayed contralateral nephrectomy (CKD) under isoflurane anesthetic. Transdermal GFR monitoring and multispectral optoacoustic tomography (MSOT) in combination with statistical analysis were used to identify and standardize variables within these models. Results Pre‐clamping anesthetic time was one of the most important predictors of AKI severity after R‐IRI. Standardizing pre‐clamping time resulted in a more predictably severe AKI model. In the CKD model, MSOT demonstrated initial improvement in renal function, followed by significant progressive reduction in function between weeks 2 and 4. Performing contralateral nephrectomy on day 14 enabled the development of CKD with minimal mortality. Conclusions Noninvasive monitoring of global and individual renal function after R‐IRI is feasible and reproducible. These techniques can facilitate refinement of kidney injury models and enable the degree of injury seen in preclinical models to be translated to those seen in the clinical setting. Thus, future therapies can be tested in a clinically relevant, noninvasive manner.
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- 2022
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9. Standard automated perimetry using size III and size V stimuli in advanced stage glaucoma: an observational cross-sectional comparative study
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Tobi Somerville, Gabriela Czanner, Fiona J Rowe, Devindra Sood, and Ishaana Sood
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Medicine - Published
- 2021
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10. Spatial and spatio-temporal statistical analyses of retinal images: a review of methods and applications
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Simon Harding, Yalin Zheng, Gabriela Czanner, Ruwanthi Kolamunnage-Dona, and Wenyue Zhu
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Ophthalmology ,RE1-994 - Abstract
Background Clinical research and management of retinal diseases greatly depend on the interpretation of retinal images and often longitudinally collected images. Retinal images provide context for spatial data, namely the location of specific pathologies within the retina. Longitudinally collected images can show how clinical events at one point can affect the retina over time. In this review, we aimed to assess statistical approaches to spatial and spatio-temporal data in retinal images. We also review the spatio-temporal modelling approaches used in other medical image types.Methods We conducted a comprehensive literature review of both spatial or spatio-temporal approaches and non-spatial approaches to the statistical analysis of retinal images. The key methodological and clinical characteristics of published papers were extracted. We also investigated whether clinical variables and spatial correlation were accounted for in the analysis.Results Thirty-four papers that included retinal imaging data were identified for full-text information extraction. Only 11 (32.4%) papers used spatial or spatio-temporal statistical methods to analyse images, others (23 papers, 67.6%) used non-spatial methods. Twenty-eight (82.4%) papers reported images collected cross-sectionally, while 6 (17.6%) papers reported analyses on images collected longitudinally. In imaging areas outside of ophthalmology, 19 papers were identified with spatio-temporal analysis, and multiple statistical methods were recorded.Conclusions In future statistical analyses of retinal images, it will be beneficial to clearly define and report the spatial distributions studied, report the spatial correlations, combine imaging data with clinical variables into analysis if available, and clearly state the software or packages used.
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- 2020
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11. Automated Classification of Changes of Direction in Soccer Using Inertial Measurement Units
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Brian Reilly, Oliver Morgan, Gabriela Czanner, and Mark A. Robinson
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change of direction movements ,Global Positioning System ,accelerometer ,gyroscope ,machine learning ,random forest ,Chemical technology ,TP1-1185 - Abstract
Changes of direction (COD) are an important aspect of soccer match play. Understanding the physiological and biomechanical demands on players in games allows sports scientists to effectively train and rehabilitate soccer players. COD are conventionally recorded using manually annotated time-motion video analysis which is highly time consuming, so more time-efficient approaches are required. The aim was to develop an automated classification model based on multi-sensor player tracking device data to detect COD > 45°. Video analysis data and individual multi-sensor player tracking data (GPS, accelerometer, gyroscopic) for 23 academy-level soccer players were used. A novel ‘GPS-COD Angle’ variable was developed and used in model training; along with 24 GPS-derived, gyroscope and accelerometer variables. Video annotation was the ground truth indicator of occurrence of COD > 45°. The random forest classifier using the full set of features demonstrated the highest accuracy (AUROC = 0.957, 95% CI = 0.956–0.958, Sensitivity = 0.941, Specificity = 0.772. To balance sensitivity and specificity, model parameters were optimised resulting in a value of 0.889 for both metrics. Similarly high levels of accuracy were observed for random forest models trained using a reduced set of features, accelerometer-derived variables only, and gyroscope-derived variables only. These results point to the potential effectiveness of the novel methodology implemented in automatically identifying COD in soccer players.
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- 2021
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12. EffUnet-SpaGen: An Efficient and Spatial Generative Approach to Glaucoma Detection
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Venkatesh Krishna Adithya, Bryan M. Williams, Silvester Czanner, Srinivasan Kavitha, David S. Friedman, Colin E. Willoughby, Rengaraj Venkatesh, and Gabriela Czanner
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glaucoma ,diagnosis ,generative model ,machine learning ,classification ,Photography ,TR1-1050 ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Current research in automated disease detection focuses on making algorithms “slimmer” reducing the need for large training datasets and accelerating recalibration for new data while achieving high accuracy. The development of slimmer models has become a hot research topic in medical imaging. In this work, we develop a two-phase model for glaucoma detection, identifying and exploiting a redundancy in fundus image data relating particularly to the geometry. We propose a novel algorithm for the cup and disc segmentation “EffUnet” with an efficient convolution block and combine this with an extended spatial generative approach for geometry modelling and classification, termed “SpaGen” We demonstrate the high accuracy achievable by EffUnet in detecting the optic disc and cup boundaries and show how our algorithm can be quickly trained with new data by recalibrating the EffUnet layer only. Our resulting glaucoma detection algorithm, “EffUnet-SpaGen”, is optimized to significantly reduce the computational burden while at the same time surpassing the current state-of-art in glaucoma detection algorithms with AUROC 0.997 and 0.969 in the benchmark online datasets ORIGA and DRISHTI, respectively. Our algorithm also allows deformed areas of the optic rim to be displayed and investigated, providing explainability, which is crucial to successful adoption and implementation in clinical settings.
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- 2021
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13. Novel Retinal Lesion in Ebola Survivors, Sierra Leone, 2016
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Paul J. Steptoe, Janet T. Scott, Julia M. Baxter, Craig K. Parkes, Rahul Dwivedi, Gabriela Czanner, Matthew J. Vandy, Fayiah Momorie, Alimamy D. Fornah, Patrick Komba, Jade Richards, Foday Sahr, Nicholas A.V. Beare, and Malcolm G. Semple
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uveitis ,retina ,Ebola ,sequelae ,viruses ,lesion ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We conducted a case–control study in Freetown, Sierra Leone, to investigate ocular signs in Ebola virus disease (EVD) survivors. A total of 82 EVD survivors with ocular symptoms and 105 controls from asymptomatic civilian and military personnel and symptomatic eye clinic attendees underwent ophthalmic examination, including widefield retinal imaging. Snellen visual acuity was
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- 2017
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14. Application of SPF moisturisers is inferior to sunscreens in coverage of facial and eyelid regions.
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Elizabeth A J Lourenco, Liam Shaw, Harry Pratt, Georgia L Duffy, Gabriela Czanner, Yalin Zheng, Kevin J Hamill, and Austin G McCormick
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Medicine ,Science - Abstract
Many moisturisers contain sun protection factors (SPF) equivalent to those found in sunscreens. However, there is a lack of research into how SPF moisturiser application compares to sunscreens in terms of coverage achieved and protection afforded. Previously we demonstrated that users incompletely covered their eyelid regions during routine sunscreen application. Here, we aimed to determine if SPF moisturiser users also displayed these tendencies. A study population of 84 participants (22 males, 62 females, age 18-57) were exposed to UV radiation and photographed using a tripod mounted UV sensitive DSLR camera on two separate visits. At visit one, images were acquired before and after applying either SPF30 sunscreen or moisturiser, then at visit two the study was repeated with the other formulation. Images were processed for facial landmark identification followed by segmentation mapping of hue saturation values to identify areas of the face that were/were not covered. Analyses revealed that application of moisturiser was significantly worse than sunscreen in terms area of the whole face missed (11.1% missed with sunscreen compared to 16.6% for SPF moisturiser p
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- 2019
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15. Accurate, fast, data efficient and interpretable glaucoma diagnosis with automated spatial analysis of the whole cup to disc profile.
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Ian J C MacCormick, Bryan M Williams, Yalin Zheng, Kun Li, Baidaa Al-Bander, Silvester Czanner, Rob Cheeseman, Colin E Willoughby, Emery N Brown, George L Spaeth, and Gabriela Czanner
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Medicine ,Science - Abstract
BackgroundGlaucoma is the leading cause of irreversible blindness worldwide. It is a heterogeneous group of conditions with a common optic neuropathy and associated loss of peripheral vision. Both over and under-diagnosis carry high costs in terms of healthcare spending and preventable blindness. The characteristic clinical feature of glaucoma is asymmetrical optic nerve rim narrowing, which is difficult for humans to quantify reliably. Strategies to improve and automate optic disc assessment are therefore needed to prevent sight loss.MethodsWe developed a novel glaucoma detection algorithm that segments and analyses colour photographs to quantify optic nerve rim consistency around the whole disc at 15-degree intervals. This provides a profile of the cup/disc ratio, in contrast to the vertical cup/disc ratio in common use. We introduce a spatial probabilistic model, to account for the optic nerve shape, we then use this model to derive a disc deformation index and a decision rule for glaucoma. We tested our algorithm on two separate image datasets (ORIGA and RIM-ONE).ResultsThe spatial algorithm accurately distinguished glaucomatous and healthy discs on internal and external validation (AUROC 99.6% and 91.0% respectively). It achieves this using a dataset 100-times smaller than that required for deep learning algorithms, is flexible to the type of cup and disc segmentation (automated or semi-automated), utilises images with missing data, and is correlated with the disc size (p = 0.02) and the rim-to-disc at the narrowest rim (pDiscussionThe spatial probabilistic algorithm is highly accurate, highly data efficient and it extends to any imaging hardware in which the boundaries of cup and disc can be segmented, thus making the algorithm particularly applicable to research into disease mechanisms, and also glaucoma screening in low resource settings.
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- 2019
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16. Correction: Accurate, fast, data efficient and interpretable glaucoma diagnosis with automated spatial analysis of the whole cup to disc profile.
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Ian J C MacCormick, Bryan M Williams, Yalin Zheng, Kun Li, Baidaa Al-Bander, Silvester Czanner, Rob Cheeseman, Colin E Willoughby, Emery N Brown, George L Spaeth, and Gabriela Czanner
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0209409.].
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- 2019
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17. Spatial Linear Mixed Effects Modelling for OCT Images: SLME Model
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Wenyue Zhu, Jae Yee Ku, Yalin Zheng, Paul C. Knox, Ruwanthi Kolamunnage-Dona, and Gabriela Czanner
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spatial modelling ,statistical analyses ,correlated data ,retinal imaging ,optical coherence tomography ,simulation ,Photography ,TR1-1050 ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Much recent research focuses on how to make disease detection more accurate as well as “slimmer”, i.e., allowing analysis with smaller datasets. Explanatory models are a hot research topic because they explain how the data are generated. We propose a spatial explanatory modelling approach that combines Optical Coherence Tomography (OCT) retinal imaging data with clinical information. Our model consists of a spatial linear mixed effects inference framework, which innovatively models the spatial topography of key information via mixed effects and spatial error structures, thus effectively modelling the shape of the thickness map. We show that our spatial linear mixed effects (SLME) model outperforms traditional analysis-of-variance approaches in the analysis of Heidelberg OCT retinal thickness data from a prospective observational study, involving 300 participants with diabetes and 50 age-matched controls. Our SLME model has a higher power for detecting the difference between disease groups, and it shows where the shape of retinal thickness profiles differs between the eyes of participants with diabetes and the eyes of healthy controls. In simulated data, the SLME model demonstrates how incorporating spatial correlations can increase the accuracy of the statistical inferences. This model is crucial in the understanding of the progression of retinal thickness changes in diabetic maculopathy to aid clinicians for early planning of effective treatment. It can be extended to disease monitoring and prognosis in other diseases and with other imaging technologies.
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- 2020
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18. Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina
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Valentina Barrera, Ian James Callum MacCormick, Gabriela Czanner, Paul Stephenson Hiscott, Valerie Ann White, Alister Gordon Craig, Nicholas Alexander Venton Beare, Lucy Hazel Culshaw, Yalin Zheng, Simon Charles Biddolph, Danny Arnold Milner, Steve Kamiza, Malcolm Edward Molyneux, Terrie Ellen Taylor, and Simon Peter Harding
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plasmodium falciparum cerebral malaria ,sequestration ,paediatric coma ,neurovasculature ,blood-retinal barrier ,malarial retinopathy ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with P. falciparum cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n = 817, OR, 95% CI: 2.90, 1.96–4.30; 3.4, 1.8–6.3, both p
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- 2018
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19. Radial shape discrimination testing for new-onset neovascular age-related macular degeneration in at-risk eyes.
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Noelia Pitrelli Vazquez, Simon P Harding, Heinrich Heimann, Gabriela Czanner, and Paul C Knox
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Medicine ,Science - Abstract
We investigated the performance of the handheld radial shape discrimination (hRSD) test in detecting the development of neovascular AMD (nAMD) in a prospective, longitudinal, observational study. Patients diagnosed with unilateral nAMD, with no nAMD in the other eye (the study eye, SE), completed the hRSD test on consecutive, routine clinic visits up to a maximum of 12, or until they were diagnosed with nAMD in the SE based on slit-lamp biomicroscopy and spectral-domain OCT assessment, with fluorescein angiography confirmation. Masked grading was carried out to confirm the diagnosis of nAMD, and to ensure no cases of nAMD were missed. Receiver operating characteristics (ROC) analysis was used to explore the diagnostic performance of the hRSD test relative to clinical diagnosis. Data were available from 179 patients of whom 19 (10.6%; "converters") developed nAMD in the SE. The mean hRSD threshold at conversion was -0.47 (95% CI -0.38 to -0.55) logMAR compared to -0.53 (-0.50 to -0.57) logMAR in 160 non-converters. hRSD threshold in the converters began to decline 190 days before diagnosis of nAMD. The ROC curve demonstrated that at an hRSD cut-off of -0.60 logMAR, sensitivity was 0.79 (0.54-0.94) with a specificity of 0.54 (0.46-0.62); positive and negative predictive values were 0.16 and 0.96 respectively. We conclude that the hRSD test has moderate sensitivity for detecting the earliest stages of nAMD in the at-risk fellow eyes of patients with unilateral nAMD, compared to clinical diagnosis. Given its relative inexpensiveness, ease of use and the inherent connectivity of the platforms it can be presented on, it may have a role in early detection of nAMD in the population at large.
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- 2018
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20. Standardization of choroidal thickness measurements using enhanced depth imaging optical coherence tomography
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Nattapon Boonarpha, Yalin Zheng, Alexandros N. Stangos, Huiqi Lu, Ankur Raj, Gabriela Czanner, Simon P. Harding, and Jayashree Nair-Sahni
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choroid ,enhanced depth imaging ,choroidal thickness ,optical coherence tomography ,diabetes ,Ophthalmology ,RE1-994 - Abstract
AIM:To describe and evaluate a standardized protocol for measuring the choroidal thickness (ChT) using enhanced depth imaging optical coherence tomography (EDI OCT).METHODS:Single 9 mm EDI OCT line scans across the fovea were used for this study. The protocol used in this study classified the EDI OCT images into four groups based on the appearance of the choroidal-scleral interface and suprachoroidal space. Two evaluation iterations of experiments were performed:first, the protocol was validated in a pilot study of 12 healthy eyes. Afterwards, the applicability of the protocol was tested in 82 eyes of patients with diabetes. Inter-observer and intra-observer agreements on image classifications were performed using Cohen’s kappa coefficient (k). Intraclass correlation coefficient (ICC) and Bland-Altman’s methodology were used for the measurement of the ChT.RESULTS:There was a moderate (k=0.42) and perfect (k=1) inter- and intra-observer agreements on image classifications from healthy eyes images and substantial (k=0.66) and almost perfect (k=0.86) agreements from diabetic eyes images. The proposed protocol showed excellent inter- and intra-observer agreements for the ChT measurements on both, healthy eyes and diabetic eyes (ICC>0.90 in all image categories). The Bland-Altman plot showed a relatively large ChT measurement agreement in the scans that contained less visible choroidal outer boundary.CONCLUSIONS:A protocol to standardize ChT measurements in EDI OCT images has been developed; the results obtained using this protocol show that the technique is accurate and reliable for routine clinical practice and research.
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- 2015
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21. UV imaging reveals facial areas that are prone to skin cancer are disproportionately missed during sunscreen application.
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Harry Pratt, Kareem Hassanin, Lee D Troughton, Gabriela Czanner, Yalin Zheng, Austin G McCormick, and Kevin J Hamill
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Medicine ,Science - Abstract
Application of sunscreen is a widely used mechanism for protecting skin from the harmful effects of UV light. However, protection can only be achieved through effective application, and areas that are routinely missed are likely at increased risk of UV damage. Here we sought to determine if specific areas of the face are missed during routine sunscreen application, and whether provision of public health information is sufficient to improve coverage. To investigate this, 57 participants were imaged with a UV sensitive camera before and after sunscreen application: first visit; minimal pre-instruction, second visit; provided with a public health information statement. Images were scored using a custom automated image analysis process designed to identify areas of high UV reflectance, i.e. missed during sunscreen application, and analysed for 5% significance. Analyses revealed eyelid and periorbital regions to be disproportionately missed during routine sunscreen application (median 14% missed in eyelid region vs 7% in rest of face, p
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- 2017
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22. Longitudinal Visuomotor Development in a Malaria Endemic Area: Cerebral Malaria and Beyond.
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Paul C Knox, Ian J C MacCormick, Emme Mbale, Macpherson Malewa, Gabriela Czanner, and Simon P Harding
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Medicine ,Science - Abstract
Paediatric cerebral malaria is the most serious complication of Plasmodium falciparum infection. While the majority recover, long-term cognitive impairment has been highlighted as a significant and neglected problem. Persistent or serious deficits in processes such as attention or behavioural inhibition should be manifest in changes to performance on oculomotor tasks. Therefore we investigated the impact of cerebral malaria on the development of reflexive pro-saccades and antisaccades. In a longitudinal study, 47 children previously admitted with retinopathy-confirmed cerebral malaria (mean age at admission 54 months), were compared with 37 local healthy controls (mean ages at first study visit 117 and 110 months respectively). In each of three or four test sessions, over a period of up to 32 months, participants completed 100 prosaccade tasks and 100 antisaccade tasks. Eye movements were recorded using infrared reflectance oculography; prosaccade, correct antisaccade and error prosaccade latency, and antisaccade directional error rate were calculated. Hierarchical linear modelling was used to investigate the effect of age and the influence of cerebral malaria on these parameters. Data were also collected from an independent, older group (mean age 183 months) of 37 local healthy participants in a separate cross-sectional study. Longitudinal data exhibited the expected decrease in latency with age for all saccade types, and a decrease in the antisaccade directional error rate. Hierarchical linear modelling confirmed that age had a statistically significant effect on all parameters (p< = 0.001). However, there were no statistically significant differences between the cerebral malaria and control groups. Combining groups, comparison with the literature demonstrated that antisaccade directional error rate for the Malawi sample was significantly higher than expected, while latencies for all saccade types were indistinguishable from published. The high directional error rate was also confirmed in the older, healthy Malawian participants from the cross sectional study. Our observation of similar oculomotor performance in cerebral malaria and control groups at long follow-up periods suggests that cerebral malaria survivors are not at a generally increased risk of persistent cognitive deficits. Our data raise questions about the prevailing hypothesis that cerebral malaria has gross impacts on the development of processes such as attention and behavioural inhibition. More importantly, our novel finding of a clear difference in antisaccade performance between all of the Malawi participants and published data suggests that the Malawian paediatric population as a whole faces serious challenges to cognitive development beyond cerebral malaria.
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- 2016
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23. Learning Active Contour Models for Medical Image Segmentation.
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Xu Chen, Bryan M. Williams 0001, Srinivasa R. Vallabhaneni, Gabriela Czanner, Rachel Williams, and Yalin Zheng
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- 2019
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24. Spatial Modelling of Retinal Thickness in Images from Patients with Diabetic Macular Oedema.
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Wenyue Zhu, Jae Yee Ku, Yalin Zheng, Paul C. Knox, Simon P. Harding, Ruwanthi Kolamunnage-Dona, and Gabriela Czanner
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- 2019
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25. Automatic detection of glaucoma via fundus imaging and artificial intelligence: A review.
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Lauren Coan, Bryan M. Williams 0001, Venkatesh Krishna Adithya, Swati Upadhyaya, Silvester Czanner, Rengaraj Venkatesh, Colin E. Willoughby, Kavitha Srinivasan, and Gabriela Czanner
- Published
- 2022
- Full Text
- View/download PDF
26. Automatic detection of glaucoma via fundus imaging and artificial intelligence: A review
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Lauren J. Coan, Bryan M. Williams, Venkatesh Krishna Adithya, Swati Upadhyaya, Ala Alkafri, Silvester Czanner, Rengaraj Venkatesh, Colin E. Willoughby, Srinivasan Kavitha, and Gabriela Czanner
- Subjects
Machine Learning ,Ophthalmology ,Artificial Intelligence ,Fundus Oculi ,Optic Disk ,Humans ,RE ,Glaucoma - Abstract
Glaucoma is a leading cause of irreversible vision impairment globally, and cases are continuously rising worldwide. Early detection is crucial, allowing timely intervention that can prevent further visual field loss. To detect glaucoma, examination of the optic nerve head via fundus imaging can be performed, at the center of which is the assessment of the optic cup and disc boundaries. Fundus imaging is non-invasive and low-cost; however, the image examination relies on subjective, time-consuming, and costly expert assessments. A timely question to ask is: "Can artificial intelligence mimic glaucoma assessments made by experts?". Specifically, can artificial intelligence automatically find the boundaries of the optic cup and disc (providing a so-called segmented fundus image) and then use the segmented image to identify glaucoma with high accuracy? We conducted a comprehensive review on artificial intelligence-enabled glaucoma detection frameworks that produce and use segmented fundus images and summarized the advantages and disadvantages of such frameworks. We identified 36 relevant papers from 2011-2021 and 2 main approaches: 1) logical rule-based frameworks, based on a set of rules; and 2) machine learning/statistical modelling based frameworks. We critically evaluated the state-of-art of the 2 approaches, identified gaps in the literature and pointed at areas for future research.
- Published
- 2023
27. Efficacy and Safety of Anticoagulants in Patients with Atrial Fibrillation and History of Falls or Risk of Falls: A Systematic Review and Multilevel Meta-Analysis
- Author
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Thibaut Galvain, Ruaraidh Hill, Sarah Donegan, Paulo Lisboa, Gregory Y. H. Lip, and Gabriela Czanner
- Subjects
Pharmacology ,Pharmacology (medical) ,Toxicology - Published
- 2022
28. OP-1 Analysis and reporting of surgically induced keratometric effect (SIKE)
- Author
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Fadi Alfaqawi, Luca Pagano, Esmaeil M Arbabi, Vito Romano, Ahmed Al-Maskari, Gabriela Czanner, and Stephen Kaye
- Published
- 2023
29. Assessing a virtual baby feeding training system.
- Author
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Alena Petrásová, Gabriela Czanner, Jassim Happa, Silvester Czanner, Dieter Wolke, and Alan Chalmers
- Published
- 2010
- Full Text
- View/download PDF
30. Investigation of the beat rate effect on frame rate for animated content.
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Vedad Hulusic, Gabriela Czanner, Kurt Debattista, Elena Sikudová, Piotr Dubla, and Alan Chalmers
- Published
- 2009
- Full Text
- View/download PDF
31. A study of visual perception: social anxiety and virtual realism.
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Joung Huem Kwon, Alan Chalmers, Silvester Czanner, Gabriela Czanner, and John A. Powell
- Published
- 2009
- Full Text
- View/download PDF
32. Adaptation to post-stroke homonymous hemianopia – a prospective longitudinal cohort study to identify predictive factors of the adaptation process
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Brinton Helliwell, Fiona J. Rowe, Claire Howard, and Gabriela Czanner
- Subjects
Adult ,030506 rehabilitation ,medicine.medical_specialty ,Process (engineering) ,Visual impairment ,Vision Disorders ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Longitudinal cohort ,Adaptation (computer science) ,Stroke ,business.industry ,Rehabilitation ,medicine.disease ,eye diseases ,Post stroke ,Hemianopsia ,Visual field loss ,Visual Fields ,medicine.symptom ,0305 other medical science ,business ,030217 neurology & neurosurgery - Abstract
To determine any factors that predict how an individual will adapt to post-stroke hemianopic visual field loss, with close monitoring of the adaptation process from an early stage.The Hemianopia Adaptation Study (HAST) is a prospective observational longitudinal cohort clinical study. Adult stroke survivors (Several baseline variables were found to be good predictors of adaptation. Three variables were associated with adaptation status at 12-weeks post-stroke: inferior % visual field, % total MAC omissions, and MAC completion time (seconds). Baseline measurements of these variables can predict the adaptation at 12 weeks with moderate to high accuracy (area under ROC curve, 0.82, 95% CI 0.74-0.90). A cut-off score of ≤25% target omissions is suggested to predict which individuals are likely to adapt by 12-weeks post-stroke following gold standard care.Adaptation to hemianopia is a personal journey with several factors being important for prediction of its presence, including MAC outcomes and extent of inferior visual field loss. A clinical recommendation is made for inclusion of the MAC as part of a functional assessment for hemianopia.Implications for rehabilitationThe mobility assessment course (MAC) should be considered as an assessment of mobility/scanning in the rehabilitation of patients with homonymous hemianopia.A cut-off score of ≤25% omissions on MAC could be employed to determine those likely to adapt to hemianopia long-term.Targeted support and therapy for patients with significant visual loss in the inferior visual field area should be considered.
- Published
- 2021
33. Dynamic models of neural spiking activity.
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Gabriela Czanner, Anna A. Dreyer, Uri T. Eden, Sylvia Wirth, Hubert H. Lim, Wendy A. Suzuki, and Emery N. Brown
- Published
- 2007
- Full Text
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34. Common Statistical Issues in Ophthalmic Research
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Catey Bunce and Gabriela Czanner
- Published
- 2022
35. Supermarket/Hypermarket Opportunistic Screening for Atrial Fibrillation (SHOPS-AF):A Mixed Methods Feasibility Study Protocol
- Author
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Ian D. Jones, Deirdre A. Lane, Robyn R. Lotto, David Oxborough, Lis Neubeck, Peter E. Penson, Gabriela Czanner, Andy Shaw, Emma Johnston Smith, Aimeris Santos, Emily E. McGinn, Aderonke Ajiboye, Nicola Town, and Gregory Y. H. Lip
- Subjects
QA75 ,T1 ,sensor devices ,Medicine (miscellaneous) ,electrocardiogram ,RT ,atrial fibrillation detection ,cardiac arrhythmia ,TA ,RA0421 ,community screening ,stroke prevention ,QA - Abstract
AIMS: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a key risk factor for ischaemic stroke. Following AF detection, treatment with oral anticoagulation can significantly lower mortality and morbidity rates associated with this risk. The availability of several hand-held devices which can detect AF may enable trained health professionals to adopt AF screening approaches which do not interfere with people's daily routines. This study aims to investigate the effectiveness of a hand-held device (the MyDiagnostick single-lead Electrocardiogram (ECG) sensor) in screening for AF when embedded into the handles of supermarket trolleys.METHODS: A mixed methods two-phase approach will be taken. The quantitative first phase will involve the recruitment of 2000 participants from a convenience sample at four large supermarkets with pharmacies. Prospective participants will be asked to conduct their shopping using a trolley embedded with a MyDiagnostick sensor. If the device identifies a participant with AF, the in-store pharmacist will be dispatched to take a manual pulse measurement and a static control sensor reading and offer a cardiologist consultation referral. When the sensor does not detect AF, a researcher will confirm the reading with a manual pulse measurement. ECGs will be compiled, and the sensitivity, specificity and positive and negative predictive values will be determined. A qualitative second phase will consist of semi-structured interviews carried out with those pharmacists and store managers in-store during the running of the trial period. These will explore the perceptions of staff regarding the merits of embedding sensors in the handles of supermarket trolleys to detect AF.CONCLUSION: This feasibility study will inform a larger future definitive trial.
- Published
- 2022
36. Visual risk factors for falls in older adults: a case-control study
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Simon P. Harding, Jignasa Mehta, David Newsham, Jude Robinson, and Gabriela Czanner
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Gerontology ,QA75 ,genetic structures ,business.industry ,Case-control study ,Falls in older adults ,Fear ,QA76 ,Contrast Sensitivity ,RC1200 ,Risk Factors ,Case-Control Studies ,Humans ,Medicine ,Geriatrics and Gerontology ,business ,Aged - Abstract
Background Falls are the second leading cause of accidental deaths worldwide mainly in older people. Older people have poor vision and published evidence suggests that it is a risk factor for falls. Less than half of falls clinics assess vision as part of the multi-factorial assessment of older adults at risk of falls despite vision being an essential input for postural stability. The aim of our study was to investigate the relationship between all clinically assessed visual functions and falls amongst older adults in a prospective observational individually age-matched case control study. Methods Visual acuity (VA), contrast sensitivity (CS), depth perception, binocular vision and binocular visual field were measured using routinely used clinical methods in falls participants (N = 83) and non-falls participants (N = 83). Data were also collected on socio-demographic factors, general health, number of medications, health quality, fear of falling and physical activity. Logistic regression analysis was carried out to determine key visual and non-visual risk factors for falls whilst adjusting for confounding covariates. Results Older adults have an increased risk of experiencing a fall if they have reduced visual function (odds ratio (OR): 3.49, 1.64-7.45, p = 0.001), specifically impaired stereoacuity worse than 85” of arc (OR: 3.4, 1.20-9.69, p = 0.02) and reduced (by 0.15 log unit) high spatial frequency CS (18 cpd) (OR:1.40, 1.12-1.80, p = 0.003). Older adults with a hearing impairment are also at higher risk of falls (OR: 3.18, 95% CI: 1.36-7.40, p = 0.007). The risk decreases with living in a less deprived area (OR: 0.74, 0.64-0.86, Conclusions The combination of social, behavioural and biological determinants are significant predictors of a fall. The non-visual risk factors include older adults, living in deprived neighbourhoods, socialising less outside of the home and those who have a hearing impairment. Impaired functional visual measures; depth perception and contrast are significant visual risk factors for falls above visual acuity.
- Published
- 2022
37. Computing Confidence Intervals for Point Process Models.
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Sridevi V. Sarma, David P. Nguyen, Gabriela Czanner, Sylvia Wirth, Matthew A. Wilson, Wendy A. Suzuki, and Emery N. Brown
- Published
- 2011
- Full Text
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38. Theory of the Snowflake Plot and Its Relations to Higher-Order Analysis Methods.
- Author
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Gabriela Czanner, Sonja Grün, and Satish Iyengar
- Published
- 2005
- Full Text
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39. The Management of Anticoagulants in Patients With Atrial Fibrillation and History of Falls or Risk of Falls: The Liverpool Af-falls Project. Protocol for a Systematic Review and Meta-analysis
- Author
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Gabriela Czanner, Thibaut Galvain, Paulo Lisboa, Gregory Y.H. Lip, Ruaraidh Hill, and Sarah Donegan
- Subjects
Protocol (science) ,medicine.medical_specialty ,Text mining ,business.industry ,Meta-analysis ,Emergency medicine ,medicine ,Atrial fibrillation ,In patient ,medicine.disease ,business - Abstract
BackgroundAtrial fibrillation affects an estimated 33 million individuals worldwide and is a major cause of stroke, heart failure, and death. Anticoagulants substantially reduces risk of stroke but are also associated with an increased risk of bleeding and especially intracranial hemorrhages which are the most feared complication. Because of this many patients are not offered anticoagulants, particularly patients at risk of falls or with history of falls. It is unclear what anticoagulant treatment these patients should be offered, and the Liverpool AF-Falls project aims to investigate this area. This protocol for a systematic review and meta-analysis aims to define what is the most appropriate anticoagulant treatment option for the for the management of atrial fibrillation patients at risk of falls or with a history of falls. MethodsThis systematic review and meta-analysis will include randomized and non-randomized studies evaluating safety and efficacy of different anticoagulant treatments (vitamin K antagonist, non-vitamin K antagonist oral anti-coagulant, anti-platelet agent and no treatment). Bibliographic databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Scopus, CINAHL, Web of Science and ClinicalTrials.gov) will be searched according to a pre-specified search strategy. Titles, abstracts, and full texts will be assessed by two independent reviewers and disagreement resolved with a third independent reviewer. The Cochrane Risk of Bias tool 2 will be used to assess risk of bias in randomized trials and the Newcastle-Ottawa-Scale tool will be used for non-randomized studies. Pairwise meta-analysis based on the fixed and random-effects models will be conducted. Publication bias will be evaluated with a funnel plot and the Egger’s test. Heterogeneity will be assessed with the I2 statistic. If conditions for indirect comparison are met and sufficient data are available, a network meta-analysis will be conducted using frequentist and Bayesian methodologies. DiscussionThis review will be the first to summarize direct and indirect evidence on safety and efficacy of anticoagulant treatments in atrial fibrillation patients at risk of falls or with history of falls. The findings will be important to patients, clinicians, and health policy-makers to inform best practice in the use of these treatments. Systematic review registrationPROSPERO registry number: CRD42020201086
- Published
- 2021
40. The management of anticoagulants in patients with atrial fibrillation and history of falls or risk of falls: protocol for a systematic review and meta-analysis
- Author
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Thibaut Galvain, Ruaraidh Hill, Sarah Donegan, Paulo Lisboa, Gregory Y. H. Lip, and Gabriela Czanner
- Subjects
QA75 ,Stroke ,Review Literature as Topic ,Meta-Analysis as Topic ,Atrial Fibrillation ,Medicine (miscellaneous) ,Administration, Oral ,Anticoagulants ,Humans ,Bayes Theorem ,RA ,RT ,Systematic Reviews as Topic - Abstract
Background Atrial fibrillation affects an estimated 33 million individuals worldwide and is a major cause of stroke, heart failure, and death. Anticoagulants substantially reduce the risk of stroke but are also associated with an increased risk of bleeding and especially intracranial hemorrhage which is the most concerning complication. Because of this, many patients are not offered anticoagulants, particularly patients at risk of falls or with a history of falls. It is unclear what anticoagulant treatment these patients should be offered. The Liverpool AF-Falls project aims to investigate this area, and this protocol for a systematic review and meta-analysis aims to define what is the most appropriate anticoagulant treatment option for the management of atrial fibrillation patients at risk of falls or with a history of falls. Methods This systematic review and meta-analysis will include randomized and non-randomized studies evaluating the safety and efficacy of different anticoagulant treatments (vitamin K antagonist and non-vitamin K antagonist oral anti-coagulant). Bibliographic databases (Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov, Embase, MEDLINE, Scopus and Web of Science) will be searched according to a pre-specified search strategy. Titles, abstracts, and full texts will be assessed by two independent reviewers and disagreements resolved with a third independent reviewer. The Cochrane Risk of Bias tool 2 (RoB 2) will be used to assess the risk of bias in randomized trials, and the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool will be used for non-randomized studies. A pairwise meta-analysis based on the fixed and random-effects models will be conducted. Publication bias will be evaluated with a funnel plot and Egger’s test. Heterogeneity will be assessed with the I2 statistic. If conditions for indirect comparison are met and sufficient data are available, a network meta-analysis will be conducted using frequentist and Bayesian methodologies. Discussion This review will be the first to summarize direct and indirect evidence on the safety and efficacy of anticoagulant treatments in atrial fibrillation patients at risk of falls or with a history of falls. The findings will be important to patients, clinicians, and health policy-makers to inform best practices in the use of these treatments. Systematic review registration PROSPERO registry number: CRD42020201086
- Published
- 2021
41. EffUnet-SpaGen: An Efficient and Spatial Generative Approach to Glaucoma Detection
- Author
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Colin E. Willoughby, Srinivasan Kavitha, Bryan M. Williams, Rengaraj Venkatesh, Gabriela Czanner, David S. Friedman, Silvester Czanner, and Venkatesh Krishna Adithya
- Subjects
Computer science ,diagnosis ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Article ,030218 nuclear medicine & medical imaging ,Convolution ,03 medical and health sciences ,0302 clinical medicine ,Photography ,Medical imaging ,Redundancy (engineering) ,medicine ,Radiology, Nuclear Medicine and imaging ,Segmentation ,generative model ,Electrical and Electronic Engineering ,TR1-1050 ,Block (data storage) ,business.industry ,Pattern recognition ,QA75.5-76.95 ,Computer Graphics and Computer-Aided Design ,Generative model ,medicine.anatomical_structure ,glaucoma ,machine learning ,classification ,Electronic computers. Computer science ,030221 ophthalmology & optometry ,Benchmark (computing) ,Computer Vision and Pattern Recognition ,Artificial intelligence ,business ,Optic disc - Abstract
Current research in automated disease detection focuses on making algorithms “slimmer” reducing the need for large training datasets and accelerating recalibration for new data while achieving high accuracy. The development of slimmer models has become a hot research topic in medical imaging. In this work, we develop a two-phase model for glaucoma detection, identifying and exploiting a redundancy in fundus image data relating particularly to the geometry. We propose a novel algorithm for the cup and disc segmentation “EffUnet” with an efficient convolution block and combine this with an extended spatial generative approach for geometry modelling and classification, termed “SpaGen” We demonstrate the high accuracy achievable by EffUnet in detecting the optic disc and cup boundaries and show how our algorithm can be quickly trained with new data by recalibrating the EffUnet layer only. Our resulting glaucoma detection algorithm, “EffUnet-SpaGen”, is optimized to significantly reduce the computational burden while at the same time surpassing the current state-of-art in glaucoma detection algorithms with AUROC 0.997 and 0.969 in the benchmark online datasets ORIGA and DRISHTI, respectively. Our algorithm also allows deformed areas of the optic rim to be displayed and investigated, providing explainability, which is crucial to successful adoption and implementation in clinical settings.
- Published
- 2021
- Full Text
- View/download PDF
42. Potential new fluoroquinolone treatments for suspected bacterial keratitis
- Author
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Rose Herbert, Mary Caddick, Tobi Somerville, Keri McLean, Shakeel Herwitker, Timothy Neal, Gabriela Czanner, Stephen Tuft, and Stephen B Kaye
- Subjects
Keratitis ,Ophthalmology ,Anti-Infective Agents ,Humans ,Microbial Sensitivity Tests ,Eye Infections, Bacterial ,Anti-Bacterial Agents ,Fluoroquinolones - Abstract
Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use. For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such asStaphylococcus aureus,Pseudomonas aeruginosa,Streptococcus pneumoniaeand several of theEnterobacteriaceae. However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. The purpose of this review is to compare the pharmacokinetics and pharmacodynamics of the FQs licensed for topical ophthalmic use with the same parameters for new generation FQs. We performed a literature review of the FQs approved for topical treatment and the new generation FQs licensed to treat systemic infections. We then compared the minimum inhibitory concentrations (MIC) of bacterial isolates and the published concentrations that FQs achieved in the cornea and aqueous. We also considered the potential suitability of new generation FQs for topical use based on their medicinal properties. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to continue with the prescribed antimicrobial, increase the frequency of application, use a combination of antimicrobials or change treatment.
- Published
- 2022
43. Diffusion kurtosis imaging for characterizing tumor heterogeneity in an intracranial rat glioblastoma model
- Author
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Clémentine Lesbats, Gabriela Czanner, Claire Louise Kelly, and Harish Poptani
- Subjects
Brain tumor ,Tumor heterogeneity ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,Cell Line, Tumor ,Cortex (anatomy) ,Fractional anisotropy ,Animals ,Medicine ,Radiology, Nuclear Medicine and imaging ,Diffusion Kurtosis Imaging ,Spectroscopy ,Brain Neoplasms ,business.industry ,medicine.disease ,Rats, Inbred F344 ,Transplantation ,Disease Models, Animal ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Kurtosis ,Molecular Medicine ,Female ,Glioblastoma ,business ,030217 neurology & neurosurgery ,Diffusion MRI - Abstract
The utility of diffusion kurtosis imaging (DKI) for assessing intra-tumor heterogeneity was evaluated in a rat model of glioblastoma multiforme. Longitudinal MRI including T2 -weighted and diffusion-weighted MRI (DWI) was performed on six female Fischer rats 8, 11 and 14 days after intracranial transplantation of F98 cells. T2 -weighted images were used to measure the tumor volumes and DWI images were used to compute diffusion tensor imaging (DTI) and DWI based parametric maps including mean diffusivity (MD), mean kurtosis (MK), axial diffusivity (AD), axial kurtosis, radial diffusivity, radial kurtosis, fractional anisotropy (FA) and kurtosis fractional anisotropy (KFA). Median values from the segmented normal contralateral cortex, tumor and edema from the diffusion parameters were compared at the three imaging time points to assess any changes in tumor heterogeneity over time. ex vivo DKI was also performed in a representative sample and compared with histology. Significant differences were observed between normal cortex, tumor and edema in both the DTI and DKI parameters. Notably, at the earliest time point MK and KFA were significantly different between normal cortex and tumor in comparison with MD or FA. Although a decreasing trend in MD, AD and FA values of the tumor were observed as the tumor grew, no significant changes in any of the DTI or DKI parameters were observed longitudinally. While DKI was equally sensitive to DTI in differentiating tumor from edema and normal brain, it was unable to detect longitudinal increases in intra-tumoral heterogeneity in the F98 model of glioblastoma multiforme.
- Published
- 2020
44. Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice
- Author
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Lisa Rambault, Katie Lee, Gabriela Czanner, George Bou-Gharios, Rob van't Hof, EG Canty-Laird, Riaz Akhtar, and Peter D. Clegg
- Subjects
medicine.medical_specialty ,Connective tissue ,Single-nucleotide polymorphism ,Heterozygote advantage ,Biology ,medicine.disease ,Compound heterozygosity ,Null allele ,Phenotype ,Endocrinology ,medicine.anatomical_structure ,Osteogenesis imperfecta ,Internal medicine ,medicine ,Type I collagen - Abstract
Type I collagen is the major structural component of bone where it exists as an (α1)2(α2)1 heterotrimer in all vertebrates. The osteogenesis imperfecta (oim) mouse model comprising solely homotrimeric (α1)3 type I collagen, due to a dysfunctional α2 chain, has a brittle bone phenotype implying that the heterotrimeric form is required for physiological bone function. However, humans with rare null alleles preventing synthesis of the α2 chain have connective tissue and cardiovascular abnormalities (cardiac valvular Ehlers Danlos Syndrome), without evident bone fragility. Conversely a prevalent human single nucleotide polymorphism leading to increased homotrimer synthesis is associated with osteoporosis. Whilst the oim line is well-studied, whether homotrimeric type I collagen is functionally equivalent to the heterotrimeric form in bone has not been demonstrated. Col1a2 null and oim mouse lines were used in this study and bones analysed by microCT and 3-point bending. RNA was also extracted from heterozygote tissues and allelic discrimination analyses performed using qRT-PCR. Here we comprehensively show for the first time that mice lacking the α2(I) chain do not have impaired bone biomechanical or structural properties, unlike oim homozygous mice. However Mendelian inheritance was affected in male mice of both lines and male mice null for the α2 chain exhibited age-related loss of condition. The brittle bone phenotype of oim homozygotes could result from detrimental effects of the oim mutant allele, however, the phenotype of oim heterozygotes is known to be less severe. We used allelic discrimination to show that the oim mutant allele is not downregulated in heterozygotes. We then tested whether gene dosage was responsible for the less severe phenotype of oim heterozygotes by generating compound heterozygotes. Data showed that compound heterozygotes had impaired bone structural properties as compared to oim heterozygotes, albeit to a lesser extent than oim homozygotes. Hence, we concluded that the presence of heterotrimeric collagen-1 in oim heterozygotes alleviates the effect of the oim mutant allele but a genetic interaction between homotrimeric collagen-1 and the oim mutant allele leads to bone fragility.
- Published
- 2020
45. How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria?
- Author
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Malcolm E. Molyneux, Michael J. Potchen, Valerie A. White, Robert S. Heyderman, Simon P. Harding, Nicholas A. V. Beare, Samuel Kampondeni, Paul Hiscott, Gabriela Czanner, Danny A. Milner, Valentina Barrera, Karl B. Seydel, Macpherson Mallewa, Terrie E. Taylor, Ian J. C. MacCormick, and Alister Craig
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Leak ,Pathology ,brain swelling ,030231 tropical medicine ,Blood–retinal barrier ,Malaria, Cerebral ,Brain Edema ,Blood–brain barrier ,Retina ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,wl_200 ,ww_270 ,fluorescein angiography ,Blood-Retinal Barrier ,wl_300 ,Immunology and Allergy ,Medicine ,Humans ,Prospective Studies ,Child ,medicine.diagnostic_test ,business.industry ,Retinal ,blood-brain barrier ,Fluorescein angiography ,malarial retinopathy ,wa_320 ,wc_750 ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,chemistry ,Cerebral Malaria ,qz_40 ,Histopathology ,cerebral malaria ,business ,ws_100 - Abstract
Background In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling, and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling. Methods We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain magnatic resonance imaging (MRI), and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria. Results Three types of retinal leakage were seen: large focal leak (LFL), punctate leak (PL), and vessel leak. The LFL and PL were associated with death (odds ratio [OR] = 13.20, 95% confidence interval [CI] = 5.21–33.78 and OR = 8.58, 95% CI = 2.56–29.08, respectively) and brain swelling (P Conclusions Blood-retina barrier breakdown occurs in 3 patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak, from barrier dysfunction, and nonperfusion were not associated with severe brain swelling but with neurological deficits, suggesting hypoxic injury in survivors.
- Published
- 2020
46. Ophthalmic statistics note 14: method agreement studies in ophthalmology: the intraclass correlation coefficient?
- Author
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Catey Bunce, Joanna Moschandreas, Gabriela Czanner, Nick Freemantle, Irene M Stratton, and Caroline J Doré
- Subjects
Measurement reproducibility ,Intraocular pressure ,Biomedical Research ,Intraclass correlation ,business.industry ,Less invasive ,Reproducibility of Results ,Sensory Systems ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Ophthalmology ,0302 clinical medicine ,Primary outcome ,Meridian (perimetry, visual field) ,Data Interpretation, Statistical ,030221 ophthalmology & optometry ,Use caution ,Optometry ,Medicine ,Humans ,sense organs ,business ,Correlation of Data ,030217 neurology & neurosurgery ,Pace - Abstract
Our previous note outlined why method agreement studies are so important in ophthalmology.1 Technology moves at a relentless pace and clinicians are keen to adopt innovative techniques that may offer benefits to their patients, such as shorter or less invasive testing, in addition to creating richer data sets that may increase the research potential of the data captured. Researchers and clinicians must, however, use caution to ensure that any differences observed between measurements made on a patient with different methods of measurement are truly due to changes in pathology rather than the method of measurement, the observer making the measurement or other variables that might influence the measurement. Even if two machines appear to report the same characteristic it is possible that one machine is measuring a different anatomical feature than another machine but using the same name. An example is in studies of keratometry and topography where the term Kmax is used to describe both the steepest meridian of the cornea in the central 3 mm (also called K2) and the power of the steepest point of the cornea.2 3 This is of particular importance in trials investigating treatments for keratoconus where Kmax may be the primary outcome measure or used to determine subject eligibility.4 We commented also in our previous note on the differences between the regulation of devices as compared with that of medicines.1 There is a tension between innovation and safety and while measurement reproducibility may not immediately be seen as relevant to harm, measurements are used to make decisions about diagnosis, progression and treatment. For example, a large change in intraocular pressure (IOP) between two visits in a child with glaucoma may indicate the need for examination under anaesthesia, while a large change in K2 readings in an individual with keratoconus might …
- Published
- 2020
47. MORTALITY OF PATIENTS WITH UVEAL MELANOMA DETECTED BY DIABETIC RETINOPATHY SCREENING
- Author
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Heinrich Heimann, Bertil Damato, Anna Praidou, Azzam Taktak, Rumana Hussain, and Gabriela Czanner
- Subjects
Adult ,Male ,Uveal Neoplasms ,medicine.medical_specialty ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Monosomy ,Internal medicine ,Cause of Death ,Medicine ,Humans ,Prospective Studies ,Young adult ,Stage (cooking) ,Prospective cohort study ,Survival rate ,Melanoma ,030304 developmental biology ,Cause of death ,Aged ,Retrospective Studies ,Aged, 80 and over ,0303 health sciences ,Diabetic Retinopathy ,business.industry ,Mortality rate ,Case-control study ,Retrospective cohort study ,General Medicine ,DNA, Neoplasm ,Middle Aged ,United Kingdom ,Survival Rate ,Ophthalmology ,Case-Control Studies ,030221 ophthalmology & optometry ,Female ,business - Abstract
Purpose To investigate whether early detection and treatment of uveal melanoma by screening was associated with a lower mortality rate. Methods Retrospective assessment of prospectively collected data comparing 132 patients with uveal melanoma referred by the National Diabetic Screening Service with 608 control patients referred through other means. Results Mean tumor diameter was smaller in the diabetic screening group (11.1 mm vs. 12.5 mm) as was tumor thickness (3.4 mm vs. 5.4 mm). The prevalence of high-risk monosomy 3 was also lower (17/40, 43% vs. 62/110, 56%). Despite a higher rate of systemic comorbidities in the patients diagnosed through screening and despite older age at diagnosis, the 5-year all-cause mortality was similar in both groups (17% vs. 20%); however, the metastatic mortality was lower in the diabetic screening group (11/132, 8% vs. 95/608, 16%). Conclusion Despite higher rates of comorbidities, the patients detected at diabetic screening had a lower 5-year mortality rate. The diabetic screening programme enabled detection and treatment of posterior uveal melanomas at an earlier stage. However, the confounding factors of lead and length time bias are not to be ignored.
- Published
- 2020
48. Spatial Modelling of Retinal Thickness in Images from Patients with Diabetic Macular Oedema
- Author
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Gabriela Czanner, Yalin Zheng, Jae Yee Ku, Wenyue Zhu, Ruwanthi Kolamunnage-Dona, Simon P. Harding, and Paul C. Knox
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Spatial contextual awareness ,medicine.medical_specialty ,medicine.diagnostic_test ,Computer science ,Linear model ,Statistical model ,Retinal ,medicine.disease ,chemistry.chemical_compound ,Optical coherence tomography ,chemistry ,Multivariate analysis of variance ,Ophthalmology ,medicine ,Statistical inference ,Maculopathy - Abstract
For the diagnosis and monitoring of retinal diseases, the spatial context of retinal thickness is highly relevant but often under-utilised. Despite the data being spatially collected, current approaches are not spatial: they involve analysing each location separately, or they analyse all image sectors together but they ignore the possible spatial correlations such as linear models, and multivariate analysis of variance (MANOVA). We propose spatial statistical inference framework for retinal images, which is based on a linear mixed effect model and which models the spatial topography via fixed effect and spatial error structures. We compare our method with MANOVA in analysis of spatial retinal thickness data from a prospective observational study, the Early Detection of Diabetic Macular Oedema (EDDMO) study involving 89 eyes with maculopathy and 168 eyes without maculopathy from 149 diabetic participants. Heidelberg Optical Coherence Tomography (OCT) is used to measure retinal thickness. MANOVA analysis suggests that the overall retinal thickness of eyes with maculopathy are not significantly different from the eyes with no maculopathy (p = 0.11), while our spatial framework can detect the difference between the two disease groups (p = 0.02). We also evaluated our spatial statistical model framework on simulated data whereby we illustrate how spatial correlations can affect the inferences about fixed effects. Our model addresses the need of correct adjustment for spatial correlations in ophthalmic images and to improve the precision of association in clinical studies. This model can be potentially extended into disease monitoring and prognosis in other diseases or imaging technologies.
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- 2020
49. Octopus 900 Automated Kinetic Perimetry versus Standard Automated Static Perimetry in Glaucoma Practice
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Tobi Somerville, Devindra Sood, Ishaana Sood, Gabriela Czanner, and Fiona J. Rowe
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,genetic structures ,Vision Disorders ,Glaucoma ,Sensitivity and Specificity ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Patient age ,Ophthalmology ,octopus (software) ,medicine ,Reaction Time ,Humans ,In patient ,Prospective Studies ,Mathematics ,Aged ,Aged, 80 and over ,Middle Aged ,medicine.disease ,Sensory Systems ,Visual field ,Automated static perimetry ,Cross-Sectional Studies ,Kinetic perimetry ,030221 ophthalmology & optometry ,Peripheral visual field loss ,Visual Field Tests ,Female ,Visual Fields ,030217 neurology & neurosurgery - Abstract
Purpose: The presence of central visual field loss does not infer the extent of peripheral visual field loss. In advanced stage glaucoma, we evaluated whether automated kinetic perimetry provided additional visual field information to that of central static perimetry. Materials and Methods: We undertook a prospective cross-sectional study of advanced-stage glaucoma defined as stages 3–4. Visual field assessment for right and left eyes was undertaken within one clinic visit using the Octopus 900 G programme and kinetic strategy. Results: We recruited 126 patients (170 eyes). Mean patient age at assessment was 55.86 years (SD 15.15). Mean kinetic reaction time was 1503.96 ms (SD 801.68). Kinetic I4e was plotted in 71% of eyes with an unadjusted area of 2513.68 degrees2 (SD 2397.91) and mean isopter radius of 23.16 degrees (SD 13.07). Kinetic I2e was plotted in 53.5% of eyes with an unadjusted area of 627.07 degrees2 (SD 1291.94) and mean isopter radius of 7.47 degrees (SD 10.59). Increased reaction time was associated with a poorer visual field (p = .001). Mean sensitivity, mean deviation and standard loss variance values on static perimetry were higher in patients who had a defined kinetic field boundary than in patients with no kinetic response to I4e stimulus (p = .0001). However, this corresponded to only small-to-medium correlation between static fields and existent kinetic fields: the presence of poor static fields did not always infer a poor kinetic visual field as poor static fields could also have good kinetic visual fields. Conclusions: Although we confirmed a lack of agreement and only a small to medium correlation between the extents of central versus peripheral visual field loss, automated kinetic perimetry did provide additional peripheral (outside the static 30-degree central field) visual field information which was clinically useful in the presence of non-informative severely defected central visual fields.
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- 2020
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50. Murine models of renal ischaemia reperfusion injury: An opportunity for refinement using non-invasive monitoring methods
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Bettina Wilm, Patricia Murray, Lauren Scarfe, Rachel Harwood, Odudu A, Joshua Bridge, Jack Sharkey, Gabriela Czanner, Simon E. Kenny, Lorenzo Ressel, and Philip A. Kalra
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medicine.medical_specialty ,business.industry ,Ischaemia-reperfusion injury ,urogenital system ,medicine.medical_treatment ,Non invasive ,Acute kidney injury ,Renal function ,medicine.disease ,urologic and male genital diseases ,Nephrectomy ,female genital diseases and pregnancy complications ,Isoflurane ,Internal medicine ,Cardiology ,Medicine ,Monitoring methods ,business ,medicine.drug ,Kidney disease - Abstract
BackgroundRenal Ischaemia Reperfusion Injury (R-IRI) can cause Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD), resulting in significant morbidity and mortality. To understand the underlying mechanisms, reproducible small-animal models of AKI and CKD are needed. We describe how innovative technologies for measuring kidney function non-invasively in small rodents allow successful refinement of the R-IRI models, and offer the unique opportunity to monitor longitudinally in individual animals the transition from AKI to CKD.MethodsMale BALB/c mice underwent bilateral renal pedicle clamping (AKI) or unilateral renal pedicle clamping with delayed contralateral nephrectomy (CKD) under isoflurane anaesthetic. Transdermal GFR monitoring and multi-spectral optoacoustic tomography in combination with statistical analysis were used to identify and standardise variables within these models.ResultsPre-clamping anaesthetic time was one of the most important predictors of AKI severity after R-IRI. Standardising pre-clamping time resulted in a more predictably severe AKI model. In the CKD model, initial improvement in renal function was followed by significant progressive reduction in function between weeks 2 and 4. Performing contralateral nephrectomy on day 14 enabled the development of CKD in a survivable way.ConclusionsNon-invasive monitoring of global and individual renal function after R-IRI is feasible, reproducible and correlates well with classical markers of injury. This facilitates refinement of kidney injury models and enables the degree of injury seen in pre-clinical models to be translated to those seen in the clinical setting. Thus, future therapies can be tested in a clinically relevant, non-invasive manner.What is already knownThe severity of Renal Ischaemia Reperfusion injury (R-IRI) varies between animal strain, gender and age. Experimental variables including temperature and clamping time are usually tightly controlled but significant variability still exists. Classically, small rodent experiments depend on endpoint evaluation of serum and histological features of disease. However, new technologies including transdermal glomerular filtration rate (GFR) monitoring and Multispectral Optoacoustic Tomography (MSOT) may enable renal function to be accurately monitored longitudinally, enabling better refinement of these models.What this study addsThis study shows that transdermal GFR measurements have reliably enabled refinement of the R-IRI model by standardisation of the duration of isoflurane prior to commencing surgery. Individual kidney function can be assessed in-vivo after unilateral R-IRI using MSOT imaging. The excretion tmax of IRDye-800 reliably represents the relative function of the injured kidney, permitting longitudinal in-vivo assessment of differential kidney function.What impact this may have on practiceThis study demonstrates the utility of two minimally-invasive in-vivo methods of monitoring kidney function which have advantages over classical methods and potentially enable fewer animals to be used in future studies. The study demonstrates refinement of bilateral and unilateral R-IRI models which will also enable a reduction in the number of animals needed for experimentation.
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- 2019
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