Optical Coherence Tomography Features of Active and Inactive Retinal Neovascularization in Proliferative Diabetic Retinopathy

PURPOSE: To describe spectral domain-optical coherence tomography features of retinal neovascularization in proliferative diabetic retinopathy and thus to identify novel signs of new vessel activity. METHODS: Retrospective, cross-sectional study. Data were collected over a 9-month period. Spectral domain optical coherence tomography scans were performed over areas of new vessel complexes (NVC) in both the disk and elsewhere, and were qualitatively graded by two masked observers. New vessel complexes activity was determined using clinical and angiographic criteria and correlated with spectral domain optical coherence tomography features. RESULTS: Forty-three eyes of 30 patients with proliferative diabetic retinopathy were included. Sixty-one NVC lesions (neovascularization of the disk—37.7%, neovascularization elsewhere—62.3%) were captured by spectral domain-optical coherence tomography and analyzed. Among them, 63.9% were classified as active and 36.1% as quiescent. Five distinctive features were identified as significantly different between active and quiescent NVC: the presence of vitreous hyperreflective dots in active NVC (P = 0.002) and the presence of epiretinal membrane (P = 0.04), inner retinal tissue contracture (P = 0.03), vitreous invasion (P = 0.02), and protrusion towards vitreous (P = 0.002) in quiescent NVC. CONCLUSION: In this exploratory study, the presence of vitreous hyperreflective dots, epiretinal membrane, inner retinal tissue contracture, vitreous invasion, and vitreous protrusion were identified as distinct signs of disease activity. Such parameters may be useful as a noninvasive imaging modality in eyes undergoing treatment for proliferative diabetic retinopathy

Genetic variation in herbivore resistance within a strawberry crop wild relative (Fragaria vesca L.)

To decrease the dependency on chemical pesticides, the resistance of cultivated strawberry to pests needs to be increased. While genetic resources within domesticated varieties are limited, wild genotypes are predicted to show high heritable variation in useful resistance traits. We collected 86 wild accessions of Fragaria vesca L. from central Sweden and screened this germplasm for antibiosis (pest survival and performance) and antixenosis (pest preference) traits active against the strawberry leaf beetle (Galerucella tenella L.). First, extensive common garden experiments were used to study antibiosis traits in the sampled plant genotypes. Heritable genetic variation among plant genotypes was found for several antibiosis traits. Second, controlled cafeteria experiments were used to test for plant genetic variation in antixenosis traits. The leaf beetles avoided egg laying on plant genotypes possessing high antibiosis. This indicates a high degree of concordance between antibiosis and antixenosis and that the beetles' egg-laying behavior optimizes the fitness of their offspring. The existence of high genetic variation in key resistance traits suggests that wild woodland strawberry contains untapped resources that are sought to reduce pesticide dependence in cultivated strawberry. Given that only a very small portion of the species' distribution area was sampled, even higher variation may be expected at the continental scale. As a whole, the genetic resources identified in this study serve to strengthen the position of woodland strawberry as a key crop wild relative

Re-evaluating diabetic papillopathy using optical coherence tomography and inner retinal sublayer analysis.

BACKGROUND/OBJECTIVES: To re-evaluate diabetic papillopathy using optical coherence tomography (OCT) for quantitative analysis of the peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell layer (mGCL) and inner nuclear layer (mINL) thickness. SUBJECTS/METHODS: In this retrospective observational case series between June 2008 and July 2019 at Moorfields Eye hospital, 24 eyes of 22 patients with diabetes and optic disc swelling with confirmed diagnosis of NAION or diabetic papillopathy by neuro-ophthalmological assessment were included for evaluation of the pRNFL, mGCL and mINL thicknesses after resolution of optic disc swelling. RESULTS: The mean age of included patients was 56.5 (standard deviation (SD) ± 14.85) years with a mean follow-up duration of 216 days. Thinning of pRNFL (mean: 66.26, SD ± 31.80 µm) and mGCL (mean volume: 0.27 mm3, SD ± 0.09) were observed in either group during follow-up, the mINL volume showed no thinning with 0.39 ± 0.05 mm3. The mean decrease in visual acuity was 4.13 (SD ± 14.27) ETDRS letters with a strong correlation between mGCL thickness and visual acuity (rho 0.74, p < 0.001). CONCLUSION: After resolution of acute optic disc swelling, atrophy of pRNFL and mGCL became apparent in all cases of diabetic papillopathy and diabetic NAION, with preservation of mINL volumes. Analysis of OCT did not provide a clear diagnostic distinction between both entities. We suggest a diagnostic overlay with the degree of pRNFL and mGCL atrophy of prognostic relevance for poor visual acuity independent of the semantics of terminology

Survival After Lung Transplantation of Cystic Fibrosis Patients Infected with Burkholderia cepacia Complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71603/1/j.1600-6143.2008.02186.x.pd

COMPARING FUNDUS FLUORESCEIN ANGIOGRAPHY AND SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE EVALUATION OF DIABETIC MACULAR PERFUSION

PURPOSE: To compare fundus fluorescein angiography (FFA) and swept-source optical coherence tomography angiography (SS-OCTA) in the evaluation of macular perfusion in diabetic patients. METHODS: Forty-one eyes (21 diabetic patients) seen at Moorfields Eye Hospital (London) over a 1-month interval underwent color fundus photography, FFA, and SS-OCTA imaging of the capillary superficial plexus using 2 different protocols: 3 × 3 mm and 4.5 × 4.5 mm. Quantitative assessment (foveal avascular zone diameters and area), qualitative analysis (macroscopic and microscopic levels) and Early Treatment Diabetic Retinopathy Study diabetic macular ischemia grading were performed. Artifacts were recorded. Intraclass correlation coefficients and weighted kappa values were calculated. RESULTS: Mean (SD) foveal avascular zone area was 0.695 (0.52) mm on FFA, 0.627 (0.54) mm on SS-OCTA 3 × 3 and 0.701 (0.54) mm on SS-OCTA 4.5 × 4.5 protocol. Intraclass correlation coefficients showed good agreement between FFA and SS-OCTA for both vertical diameter and foveal avascular zone area measurements. The agreement between SS-OCTA 3 × 3 and 4.5 × 4.5 was good for all quantitative measurements. Weighted kappa for diabetic macular ischemia grading showed low to fair agreement between FFA and SS-OCTA, whereas the agreement was good between two different SS-OCTA protocols. CONCLUSION: Swept-source OCTA is a reproducible technique in the assessment of macular perfusion in diabetic patients with special regards to foveal avascular zone analysis. The agreement with FFA is limited especially for diabetic macular ischemia grading. Fundus fluorescein angiography is more sensitive in identifying microaneurysms

Multidimensional sexual perfectionism and female sexual function: A longitudinal investigation

Research on multidimensional sexual perfectionism differentiates four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. Self-oriented sexual perfectionism reflects perfectionistic standards people apply to themselves as sexual partners; partner-oriented sexual perfectionism reflects perfectionistic standards people apply to their sexual partner; partner-prescribed sexual perfectionism reflects people’s beliefs that their sexual partner imposes perfectionistic standards on them; and socially prescribed sexual perfectionism reflects people’s beliefs that society imposes such standards on them. Previous studies found partner-prescribed and socially prescribed sexual perfectionism to be maladaptive forms of sexual perfectionism associated with a negative sexual self-concept and problematic sexual behaviors, but only examined cross-sectional relationships. The present article presents the first longitudinal study examining whether multidimensional sexual perfectionism predicts changes in sexual self-concept and sexual function over time. A total of 366 women aged 17-69 years completed measures of multidimensional sexual perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and female sexual function (cross-sectional data). Three to six months later, 164 of the women completed the same measures again (longitudinal data). Across analyses, partner-prescribed sexual perfectionism emerged as the most maladaptive form of sexual perfectionism. In the cross-sectional data, partner-prescribed sexual perfectionism showed positive relationships with sexual anxiety, sexual problem self-blame, and intercourse pain and negative relationships with sexual esteem, desire, arousal, lubrication, and orgasmic function. In the longitudinal data, partner-prescribed sexual perfectionism predicted increases in sexual anxiety and decreases in sexual esteem, arousal, and lubrication over time. The findings suggest that partner-prescribed sexual perfectionism contributes to women’s negative sexual self-concept and female sexual dysfunction

Joining the dots: Conditional pass and programmatic assessment enhances recognition of problems with professionalism and factors hampering student progress

<p>Abstract</p> <p>Background</p> <p>Programmatic assessment that looks across a whole year may contribute to better decisions compared with those made from isolated assessments alone. The aim of this study is to describe and evaluate a programmatic system to handle student assessment results that is aligned not only with learning and remediation, but also with defensibility. The key components are standards based assessments, use of "Conditional Pass", and regular progress meetings.</p> <p>Methods</p> <p>The new assessment system is described. The evaluation is based on years 4-6 of a 6-year medical course. The types of concerns staff had about students were clustered into themes alongside any interventions and outcomes for the students concerned. The likelihoods of passing the year according to type of problem were compared before and after phasing in of the new assessment system.</p> <p>Results</p> <p>The new system was phased in over four years. In the fourth year of implementation 701 students had 3539 assessment results, of which 4.1% were Conditional Pass. More in-depth analysis for 1516 results available from 447 students revealed the odds ratio (95% confidence intervals) for failure was highest for students with problems identified in more than one part of the course (18.8 (7.7-46.2) p < 0.0001) or with problems with professionalism (17.2 (9.1-33.3) p < 0.0001). The odds ratio for failure was lowest for problems with assignments (0.7 (0.1-5.2) NS). Compared with the previous system, more students failed the year under the new system on the basis of performance during the year (20 or 4.5% compared with four or 1.1% under the previous system (p < 0.01)).</p> <p>Conclusions</p> <p>The new system detects more students in difficulty and has resulted in less "failure to fail". The requirement to state conditions required to pass has contributed to a paper trail that should improve defensibility. Most importantly it has helped detect and act on some of the more difficult areas to assess such as professionalism.</p

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma

Background Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism. Case presentation A 65-year-old patient with metastatic melanoma who progressed through two immunotherapy strategies with immune checkpoint inhibitor antibodies was enrolled in a phase I study (NCT02285101) and treated with 2 mg/kg intravenously, weekly pegylated recombinant arginase (BCT-100). The patient experienced no toxicities > grade 2 and entered a complete remission which is sustained for over 30 months. RNA-sequencing identified a number of transcriptomic pathway alterations compared to control samples. The tumour had absent expression of the recycling enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC) indicating a state of arginine auxotrophy, which was reconfirmed by immunohistochemistry, and validation in a larger cohort of melanoma tumour samples. Conclusions Targeting arginine metabolism with therapeutic arginase in arginine auxotrophic melanoma can be an effective salvage for the treatment of patients who fail immunotherapy

Validation of Results from Knowledge Discovery: Mass Density as a Predictor of Breast Cancer

The purpose of our study is to identify and quantify the association between high breast mass density and breast malignancy using inductive logic programming (ILP) and conditional probabilities, and validate this association in an independent dataset. We ran our ILP algorithm on 62,219 mammographic abnormalities. We set the Aleph ILP system to generate 10,000 rules per malignant finding with a recall >5% and precision >25%. Aleph reported the best rule for each malignant finding. A total of 80 unique rules were learned. A radiologist reviewed all rules and identified potentially interesting rules. High breast mass density appeared in 24% of the learned rules. We confirmed each interesting rule by calculating the probability of malignancy given each mammographic descriptor. High mass density was the fifth highest ranked predictor. To validate the association between mass density and malignancy in an independent dataset, we collected data from 180 consecutive breast biopsies performed between 2005 and 2007. We created a logistic model with benign or malignant outcome as the dependent variable while controlling for potentially confounding factors. We calculated odds ratios based on dichomotized variables. In our logistic regression model, the independent predictors high breast mass density (OR 6.6, CI 2.5–17.6), irregular mass shape (OR 10.0, CI 3.4–29.5), spiculated mass margin (OR 20.4, CI 1.9–222.8), and subject age (β = 0.09, p < 0.0001) significantly predicted malignancy. Both ILP and conditional probabilities show that high breast mass density is an important adjunct predictor of malignancy, and this association is confirmed in an independent data set of prospectively collected mammographic findings