Active and inactive microaneurysms identified and characterized by structural and angiographic optical coherence tomography

Purpose: To characterize flow status within microaneurysms (MAs) and quantitatively investigate their relations with regional macular edema in diabetic retinopathy (DR). Design: Retrospective, cross-sectional study. Participants: A total of 99 participants, including 23 with mild nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, 17 with proliferative DR. Methods: In this study, 3x3-mm optical coherence tomography (OCT) and OCT angiography (OCTA) scans with a 400x400 sampling density from one eye of each participant were obtained using a commercial OCT system. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as active if the flow signal was present in the OCTA channel. Then active MAs were further classified into fully active and partially active MAs based on the flow perfusion status of MA on en face OCTA. The presence of retinal fluid near MAs was compared between active and inactive types. We also compared OCT-based MA detection to fundus photography (FP) and fluorescein angiography (FA)-based detection. Results: We identified 308 MAs (166 fully active, 88 partially active, 54 inactive) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified straddle the inner nuclear layer and outer plexiform layer. Compared to partially active and inactive MAs, fully active MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully active MAs than with partially active and inactive MAs. OCT/OCTA detected all MAs found on FP. While not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP. Conclusions: Co-registered OCT and OCTA can characterize MA activities, which could be a new means to study diabetic macular edema pathophysiology

Risk factors for major adverse cardiovascular events in phase III and long‐term extension studies of tofacitinib in patients with rheumatoid arthritis

Objective: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). This study was undertaken to evaluate the risk of major adverse cardiovascular events (MACE) in patients with RA receiving tofacitinib. Methods: Data were pooled from patients with moderately to severely active RA receiving ≥1 tofacitinib dose in 6 phase III and 2 long‐term extension studies over 7 years. MACE (myocardial infarction, stroke, cardiovascular death) were independently adjudicated. Cox regression models were used to evaluate associations between baseline variables and time to first MACE. Following 24 weeks of tofacitinib, changes in variables and time to future MACE were evaluated after adjusment for age, baseline values, and time‐varying tofacitinib dose. Hazard ratios and 95% confidence intervals were calculated. Results: Fifty‐two MACE occurred in 4,076 patients over 12,873 patient‐years of exposure (incidence rate 0.4 patients with events per 100 patient‐years). In univariable analyses of baseline variables, traditional cardiovascular risk factors and glucocorticoid and statin use were associated with MACE risk; disease activity and inflammation measures were not. In subsequent multivariable analyses, baseline age, hypertension, and the total cholesterol to high‐density lipoprotein (HDL) cholesterol ratio remained significantly associated with risk of MACE. After 24 weeks of treatment, an increase in HDL cholesterol and a decrease in the total to HDL cholesterol were associated with decreased MACE risk; changes in total cholesterol, low‐density lipoprotein (LDL) cholesterol, and disease activity measures were not. Increased erythrocyte sedimentation rates trended with increased future MACE risk. Conclusion: In this post hoc analysis, after 24 weeks of tofacitinib treatment, increased HDL cholesterol, but not increased LDL cholesterol or total cholesterol, appeared to be associated with lower future MACE risk. Further data are needed to test the cardiovascular safety of tofacitinib

Interpretable Diabetic Retinopathy Diagnosis based on Biomarker Activation Map

Deep learning classifiers provide the most accurate means of automatically diagnosing diabetic retinopathy (DR) based on optical coherence tomography (OCT) and its angiography (OCTA). The power of these models is attributable in part to the inclusion of hidden layers that provide the complexity required to achieve a desired task. However, hidden layers also render algorithm outputs difficult to interpret. Here we introduce a novel biomarker activation map (BAM) framework based on generative adversarial learning that allows clinicians to verify and understand classifiers decision-making. A data set including 456 macular scans were graded as non-referable or referable DR based on current clinical standards. A DR classifier that was used to evaluate our BAM was first trained based on this data set. The BAM generation framework was designed by combing two U-shaped generators to provide meaningful interpretability to this classifier. The main generator was trained to take referable scans as input and produce an output that would be classified by the classifier as non-referable. The BAM is then constructed as the difference image between the output and input of the main generator. To ensure that the BAM only highlights classifier-utilized biomarkers an assistant generator was trained to do the opposite, producing scans that would be classified as referable by the classifier from non-referable scans. The generated BAMs highlighted known pathologic features including nonperfusion area and retinal fluid. A fully interpretable classifier based on these highlights could help clinicians better utilize and verify automated DR diagnosis.Comment: 12 pages, 8 figure

Extremal Sasakian Geometry on T2×S3T^2\times S^3 and Related Manifolds

We prove the existence of extremal Sasakian structures occurring on a countably infinite number of distinct contact structures on $T^2\times S^3$ and certain related manifolds. These structures occur in bouquets and exhaust the Sasaki cones in all except one case in which there are no extremal metrics.Comment: 35 pages, clarifications made and typos corrected in revised version, further corrections made, slight change in title, to appear in Compositio Mathematic

Hamiltonian 2-forms in Kahler geometry, III Extremal metrics and stability

This paper concerns the explicit construction of extremal Kaehler metrics on total spaces of projective bundles, which have been studied in many places. We present a unified approach, motivated by the theory of hamiltonian 2-forms (as introduced and studied in previous papers in the series) but this paper is largely independent of that theory. We obtain a characterization, on a large family of projective bundles, of those `admissible' Kaehler classes (i.e., the ones compatible with the bundle structure in a way we make precise) which contain an extremal Kaehler metric. In many cases, such as on geometrically ruled surfaces, every Kaehler class is admissible. In particular, our results complete the classification of extremal Kaehler metrics on geometrically ruled surfaces, answering several long-standing questions. We also find that our characterization agrees with a notion of K-stability for admissible Kaehler classes. Our examples and nonexistence results therefore provide a fertile testing ground for the rapidly developing theory of stability for projective varieties, and we discuss some of the ramifications. In particular we obtain examples of projective varieties which are destabilized by a non-algebraic degeneration.Comment: 40 pages, sequel to math.DG/0401320 and math.DG/0202280, but largely self-contained; partially replaces and extends math.DG/050151

Gratitude, resignation and the desire for dignity: lived experience of food charity recipients and their recommendations for improvement, Perth, Western Australia

ObjectiveThe present study explored recipients’ perceptions of food charity and their suggested improvements in inner-city Perth, Western Australia.DesignIn-depth interviews were conducted with charitable food service (CFS) recipients. Transcripts were thematically analysed using a phenomenological approach.SettingInterviews were conducted at two CFS in inner-city Perth.SubjectsFourteen adults.ResultsThe recipients’ journeys to a reliance on CFS were varied and multifactorial, with poverty, medical issues and homelessness common. The length of time recipients had relied on food charity ranged from 8 months to over 40 years. Most were ‘grateful yet resigned’, appreciative of any food and resigned to the poor quality, monotony and their unmet individual preferences. They wanted healthier food, more variety and better quality. Accessing services was described as a ‘full-time job’ fraught with unreliable information and transport difficulties. They called for improved information and assistance with transport. ‘Eroded dignity’ resulted from being fed without any choice and queuing for food in public places, often in a volatile environment. ‘Food memories and inclusion’ reflected a desire for commensality. Recipients suggested services offer choice and promote independence, focusing on their needs both physical and social.ConclusionsAlthough grateful, long-term CFS recipients described what constitutes a voluntary failure. Their service improvement recommendations can help meet their nutritional and social needs. A successful CFS provides a food service that prioritises nutritious, good-quality food and individual need, while promoting dignity and social inclusion, challenging in the current Australian context

Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye

Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.National Institutes of Health (U.S.) (Grant R01-EY023285)National Institutes of Health (U.S.) (Grant R01-EY024544)National Institutes of Health (U.S.) (Grant DP3 DK104397)National Institutes of Health (U.S.) (Grant R01-EY11289)National Institutes of Health (U.S.) (Grant K08-EY021186)National Institutes of Health (U.S.) (Grant T32-EY23211)National Institutes of Health (U.S.) (Grant P30-EY010572)Clinical and Translational Science Award Grant UL1TR000128Research to Prevent Blindness, Inc. (United States) (Grant and Career Development Award CD-NMT-0914-0659-OHSU)United States. Air Force Office of Scientific Research (Foundation Fighting Blindness Career Development Award FA9550-10-1-0551)German Research Foundation (Grant DFG-HO-1791/11-1)German Research Foundation (Grant DFG-GSC80-SAOT

Patients' online access to their electronic health records and linked online services: a systematic review in primary care

Background Online access to medical records by patients can potentially enhance provision of patient-centred care and improve satisfaction. However, online access and services may also prove to be an additional burden for the healthcare provider. Aim To assess the impact of providing patients with access to their general practice electronic health records (EHR) and other EHR-linked online services on the provision, quality, and safety of health care. Design and setting A systematic review was conducted that focused on all studies about online record access and transactional services in primary care. Method Data sources included MEDLINE, Embase, CINAHL, Cochrane Library, EPOC, DARE, King’s Fund, Nuffield Health, PsycINFO, OpenGrey (1999–2012). The literature was independently screened against detailed inclusion and exclusion criteria; independent dual data extraction was conducted, the risk of bias (RoB) assessed, and a narrative synthesis of the evidence conducted. Results A total of 176 studies were identified, 17 of which were randomised controlled trials, cohort, or cluster studies. Patients reported improved satisfaction with online access and services compared with standard provision, improved self-care, and better communication and engagement with clinicians. Safety improvements were patient-led through identifying medication errors and facilitating more use of preventive services. Provision of online record access and services resulted in a moderate increase of e-mail, no change on telephone contact, but there were variable effects on face-to-face contact. However, other tasks were necessary to sustain these services, which impacted on clinician time. There were no reports of harm or breaches in privacy. Conclusion While the RoB scores suggest many of the studies were of low quality, patients using online services reported increased convenience and satisfaction. These services positively impacted on patient safety, although there were variations of record access and use by specific ethnic and socioeconomic groups. Professional concerns about privacy were unrealised and those about workload were only partly so