Supervised machine learning based multi-task artificial intelligence classification of retinopathies

Artificial intelligence (AI) classification holds promise as a novel and affordable screening tool for clinical management of ocular diseases. Rural and underserved areas, which suffer from lack of access to experienced ophthalmologists may particularly benefit from this technology. Quantitative optical coherence tomography angiography (OCTA) imaging provides excellent capability to identify subtle vascular distortions, which are useful for classifying retinovascular diseases. However, application of AI for differentiation and classification of multiple eye diseases is not yet established. In this study, we demonstrate supervised machine learning based multi-task OCTA classification. We sought 1) to differentiate normal from diseased ocular conditions, 2) to differentiate different ocular disease conditions from each other, and 3) to stage the severity of each ocular condition. Quantitative OCTA features, including blood vessel tortuosity (BVT), blood vascular caliber (BVC), vessel perimeter index (VPI), blood vessel density (BVD), foveal avascular zone (FAZ) area (FAZ-A), and FAZ contour irregularity (FAZ-CI) were fully automatically extracted from the OCTA images. A stepwise backward elimination approach was employed to identify sensitive OCTA features and optimal-feature-combinations for the multi-task classification. For proof-of-concept demonstration, diabetic retinopathy (DR) and sickle cell retinopathy (SCR) were used to validate the supervised machine leaning classifier. The presented AI classification methodology is applicable and can be readily extended to other ocular diseases, holding promise to enable a mass-screening platform for clinical deployment and telemedicine.Comment: Supplemental material attached at the en

Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery.

BACKGROUND: Macular oedema (MO) is the accumulation of extracellular fluid in the central retina (the macula). It may occur after cataract surgery and may give rise to poor visual outcome, with reduced visual acuity and distortion of the central vision. MO is often self-limiting with spontaneous resolution, but a small proportion of people with chronic persistent MO may be difficult to treat. Chronic oedema may lead to the formation of cystic spaces in the retina termed 'cystoid macular oedema' (CMO). Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in cataract surgery and may reduce the chances of developing MO. OBJECTIVES: The aim of this review is to answer the question: is there evidence to support the prophylactic use of topical NSAIDs either in addition to, or instead of, topical steroids postoperatively to reduce the incidence of macular oedema (MO) and associated visual morbidity. SEARCH METHODS: We searched a number of electronic databases including CENTRAL, MEDLINE and Embase. Date last searched 2 September 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which adult participants had undergone surgery for age-related cataract. We included participants irrespective of their baseline risk of MO, in particular we included people with diabetes and uveitis. We included trials of preoperative and/or postoperative topical NSAIDs in conjunction with postoperative topical steroids. The comparator was postoperative topical steroids alone. A secondary comparison was preoperative and/or postoperative topical NSAIDs alone versus postoperative topical steroids alone. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed risk of bias and extracted data using standard methods expected by Cochrane. We pooled data using a random-effects model. We graded the certainty of the evidence using GRADE and considered the following: risk of bias of included studies, precision of the effect estimate, consistency of effects between studies, directness of the outcome measure and publication bias. MAIN RESULTS: We identified 34 studies that were conducted in the Americas, Europe, the Eastern Mediterranean region and South-East Asia. Over 5000 people were randomised in these trials. The majority of studies enrolled one eye per participant; a small subset (4 trials) enrolled a proportion of people with bilateral surgery. Twenty-eight studies compared NSAIDs plus steroids with steroids alone. Six studies compared NSAIDs with steroids. A variety of NSAIDs were used, including ketorolac, diclofenac, nepafenac, indomethacin, bromfenac, flurbiprofen and pranopfen. Follow-up ranged from one to 12 months. In general, the studies were poorly reported. We did not judge any of the studies at low risk of bias in all domains. Six studies were funded by industry, seven studies were funded from non-industry sources, and the rest of the studies did not report the source of funding.There was low-certainty evidence that people receiving topical NSAIDs in combination with steroids may have a lower risk of poor vision due to MO at three months after cataract surgery compared with people receiving steroids alone (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.23 to 0.76; eyes = 1360; studies = 5; I2 = 5%). We judged this to be low-certainty evidence because of risk of bias in the included studies and indirectness, as the extent of visual loss was not always clear. Only one study reported poor vision due to MO at 12 months and we judged this to be very low-certainty evidence as there were only two events. Quality of life was only reported in one of the 34 studies comparing NSAIDs plus steroids versus steroids alone, and it was not fully reported, other than to comment on lack of differences between groups. There was evidence of a reduced risk of MO with NSAIDs at three months after surgery, but we judged this to be low-certainty due to risk of bias and publication bias (RR 0.40, 95% CI 0.32 to 0.49; eyes = 3638; studies = 21). There was inconsistent evidence on central retinal thickness at three months (I2 = 87%). Results ranged from -30.9 µm in favour of NSAIDs plus steroids to 7.44 µm in favour of steroids alone. Similarly, data on best corrected visual acuity (BCVA) were inconsistent, but nine out of 10 trials reporting this outcome found between-group differences in visual acuity of less than 0.1 logMAR.None of the six studies comparing NSAIDs alone with steroids reported on poor vision due to MO at three or 12 months. There was low-certainty evidence that central retinal thickness was lower in the NSAIDs group at three months (mean difference (MD) -22.64 µm, 95% CI -38.86 to -6.43; eyes = 121; studies = 2). Five studies reported on MO and showed a reduced risk with NSAIDs, but we judged this evidence to be of low-certainty (RR 0.27, 95% CI 0.18 to 0.41; eyes = 520). Three studies reported BCVA at three months and the results of these trials were inconsistent, but all three studies found differences of less than 0.1 logMAR between groups.We did not note any major adverse events - the main consistent observation was burning or stinging sensation with the use of NSAIDs. AUTHORS' CONCLUSIONS: Using topical NSAIDs may reduce the risk of developing macular oedema after cataract surgery, although it is possible that current estimates as to the size of this reduction are exaggerated. It is unclear the extent to which this reduction has an impact on the visual function and quality of life of patients. There is little evidence to suggest any important effect on vision after surgery. The value of adding topical NSAIDs to steroids, or using them as an alternative to topical steroids, with a view to reducing the risk of poor visual outcome after cataract surgery is therefore uncertain. Future trials should address the remaining clinical uncertainty of whether prophylactic topical NSAIDs are of benefit, particularly with respect to longer-term follow-up (at least to 12 months), and should be large enough to detect reduction in the risk of the outcome of most interest to patients, which is chronic macular oedema leading to visual loss

Designing for Effective and Safe Multidisciplinary Primary Care Teamwork: Using the Time of COVID-19 as a Case Study

Effective medical teamwork can improve the effectiveness and experience of care for staff and patients, including safety. Healthcare organizations, and especially primary care clinics, have sought to improve medical teamwork through improved layout and design, moving staff into shared multidisciplinary team rooms. While co-locating staff has been shown to increase communi-cation, successful designs balance four teamwork needs: face-to-face communications; situational awareness; heads-down work; perception of teamness. However, precautions for COVID-19 make it more difficult to conduct face-to-face communications. In this paper we describe a model for un-derstanding how layout affects these four teamwork needs and describe how the perception of teamwork by staff changed after COVID-19 precautions were put in place. Observations, interviews and two standard surveys were conducted in two primary care clinics before COVID-19 and again in 2021 after a year of precautions. In general, staff felt more isolated and found it more difficult to conduct brief consults, though these perceptions varied by role. RNs, who spent more time on the phone, found it convenient to work part time-from home, while medical assistants found it more difficult to find providers in the distanced clinics. These cases suggest some important considera-tions for future clinic designs, including greater physical transparency that also allow for physical separation and more spaces for informal communication that are distanced from workstations

Clinical consequences of a miscalibrated digoxin immunoassay

A routine audit revealed that the analytical method used to measure digoxin concentrations by our statewide pathology provider in 2009 was underestimating digoxin concentrations by 10%. The assay was recalibrated by the manufacturer in 2010, but clinical outcomes of the underestimation were never measured. This is a pilot study to describe the prescribing behavior around out-of-range digoxin concentrations and to assess whether miscalibrated digoxin immunoassays contribute to clinically relevant effects, as measured by inappropriate alterations in digoxin doses.About 30,000 digoxin concentrations across the State Hospital system were obtained in 2 periods before and after recalibration of the digoxin assay. Digoxin concentration means were calculated and compared and were statistically significantly different. Subsequently, a single-centered retrospective review of 50 randomly chosen charts was undertaken to study the clinical implications of the underestimated concentrations.Mean digoxin concentrations for 2009 and 2011 were significantly different by 8.8% (confidence interval, 7.0%-10.6%). After recalculating the 2009 concentrations to their "corrected" values, there was a 16% increase in the number of concentrations within the range when compared with the 2011 concentrations (41.48% versus 48.04%). However, overall, this did not cause unnecessary dose changes in patients who were "borderline" or outside the therapeutic range when compared with controls (P = 0.10). The majority of decisions were based on the clinical impression rather than concentration alone (85.1% versus 14.9%), even when the concentration was outside the "therapeutic range."Although recalculating digoxin concentrations measured during 2009 to their corrected values produced a significant change in concentration and values inside and outside the range, this does not seem to have had an influence on patient treatment. Rather, clinicians tended to use the clinical impression to dose digoxin

First Results from the Mojave Volatiles Prospector (MVP) Field Campaign, a Lunar Polar Rover Mission Analog

The Mojave Volatiles Prospector (MVP) project is a science-driven field program with the goal to produce critical knowledge for conducting robotic exploration of the Moon. MVP will feed science, payload, and operational lessons learned to the development of a real-time, short-duration lunar polar volatiles prospecting mission. MVP achieves these goals through a simulated lunar rover mission to investigate the composition and distribution of surface and subsurface volatiles in a natural and a priori unknown environment within the Mojave Desert, improving our understanding of how to find, characterize, and access volatiles on the Moon. The MVP field site is the Mojave Desert, selected for its low, naturally occurring water abundance. The Mojave typically has on the order of 2-6% water, making it a suitable lunar analog for this field test. MVP uses the Near Infrared and Visible Spectrometer Subsystem (NIRVSS), Neutron Spectrometer Subsystem (NSS), and a downward facing GroundCam camera on the KREX-2 rover to investigate the relationship between the distribution of volatiles and soil crust variation. Through this investigation, we mature robotic in situ instruments and concepts of instrument operations, improve ground software tools for real time science, and carry out publishable research on the water cycle and its connection to geomorphology and mineralogy in desert environments. A lunar polar rover mission is unlike prior space missions and requires a new concept of operations. The rover must navigate 3-5 km of terrain and examine multiple sites in in just ~6 days. Operational decisions must be made in real time, requiring constant situational awareness, data analysis and rapid turnaround decision support tools. This presentation will focus on the first science results and operational architecture findings from the MVP field deployment relevant to a lunar polar rover mission

Overview of NASA FINESSE (Field Investigations to Enable Solar System Science and Exploration) Science and Exploration Results

NASA's FINESSE (Field Investigations to Enable Solar System Science and Exploration) project is focused on a science and exploration field-based research program to generate strategic knowledge in preparation for human and robotic exploration of other planetary bodies including our moon, Mars' moons Phobos and Deimos, and near-Earth asteroids. Scientific study focuses on planetary volcanism (e.g., the formation of volcanoes, evolution of magma chambers and the formation of multiple lava flow types, as well as the evolution and entrapment of volatile chemicals) and impact cratering (impact rock modification, cratering mechanics, and the chronologic record). FINESSE conducts multiple terrestrial field campaigns (Craters of the Moon National Monument and Preserve in Idaho for volcanics, and West Clearwater Impact Structure in Canada for impact studies) to study such features as analogs relevant to our moon, Phobos, Deimos, and asteroids. Here we present the science and exploration results from two deployments to Idaho (2014, 2015) and our first deployment to Canada (2014). FINESSE was selected as a research team by NASA's Solar System Exploration Research Virtual Institute (SSERVI). SSERVI is a joint effort by NASA's Science Mission Directorate (SMD) and Human Exploration and Operations Mission Directorate (HEOMD)

Chemokine Receptor 5 Δ32 Allele in Patients with Severe Pandemic (H1N1) 2009

Because chemokine receptor 5 (CCR5) may have a role in pulmonary immune response, we explored whether patients with severe pandemic (H1N1) 2009 were more likely to carry the CCR5Δ32 allele than were members of the general population. We found a large proportion of heterozygosity for the CCR5Δ32 allele among white patients with severe disease

Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques

Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients

Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology

ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo . Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4 + T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication. IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes significant outbreaks of viral arthralgia. Studies with CHIKV and other alphaviruses demonstrated that the opal termination codon within nsP3 is highly conserved. However, some strains of CHIKV and other alphaviruses contain mutations in the opal termination codon. These mutations alter the virulence of related alphaviruses in mammalian and mosquito hosts. Here, we report that a clinical isolate of a CHIKV strain from the recent outbreak in the Caribbean islands contains a mixture of viruses encoding either the opal termination codon or an arginine mutation. Mutating the opal stop codon to an arginine residue attenuates CHIKV-induced disease in a mouse model. Compared to infection with the opal-containing parental virus, infection with the arginine mutant causes limited swelling and inflammation, as well as dampened recruitment of immune mediators of pathology, including CD4 + T cells and NK cells. We propose that the opal termination codon plays an essential role in the induction of severe CHIKV disease

Incidence of community-acquired lower respiratory tract infections and pneumonia among older adults in the United Kingdom: a population-based study.

Community-acquired lower respiratory tract infections (LRTI) and pneumonia (CAP) are common causes of morbidity and mortality among those aged ≥65 years; a growing population in many countries. Detailed incidence estimates for these infections among older adults in the United Kingdom (UK) are lacking. We used electronic general practice records from the Clinical Practice Research Data link, linked to Hospital Episode Statistics inpatient data, to estimate incidence of community-acquired LRTI and CAP among UK older adults between April 1997-March 2011, by age, sex, region and deprivation quintile. Levels of antibiotic prescribing were also assessed. LRTI incidence increased with fluctuations over time, was higher in men than women aged ≥70 and increased with age from 92.21 episodes/1000 person-years (65-69 years) to 187.91/1000 (85-89 years). CAP incidence increased more markedly with age, from 2.81 to 21.81 episodes/1000 person-years respectively, and was higher among men. For both infection groups, increases over time were attenuated after age-standardisation, indicating that these rises were largely due to population aging. Rates among those in the most deprived quintile were around 70% higher than the least deprived and were generally higher in the North of England. GP antibiotic prescribing rates were high for LRTI but lower for CAP (mostly due to immediate hospitalisation). This is the first study to provide long-term detailed incidence estimates of community-acquired LRTI and CAP in UK older individuals, taking person-time at risk into account. The summary incidence commonly presented for the ≥65 age group considerably underestimates LRTI/CAP rates, particularly among older individuals within this group. Our methodology and findings are likely to be highly relevant to health planners and researchers in other countries with aging populations