Interventions for central serous chorioretinopathy: a network meta-analysis.

BACKGROUND: Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. OBJECTIVES: To compare the relative effectiveness of interventions for central serous chorioretinopathy. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. SELECTION CRITERIA: Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model. MAIN RESULTS: We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked.The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC.Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) -0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted.Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD -0.10 logMAR, 95% CI -0.18 to -0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted.Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI -0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants).Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD -0.20 logMAR, 95% CI -0.30 to -0.11; 45 participants). There were no significant adverse effects noted.Other comparisons were largely inconclusive.We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified. AUTHORS' CONCLUSIONS: CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials

Breastfeeding, the use of docosahexaenoic acid-fortified formulas in infancy and neuropsychological function in childhood

OBJECTIVE: To investigate the relation between breastfeeding, use of docosahexaenoic acid (DHA)-fortified formula and neuropsychological function in children. DESIGN: Prospective cohort study. SETTING: Southampton, UK. SUBJECTS: 241 children aged 4 years followed up from birth. MAIN OUTCOME MEASURES: IQ measured by the Wechsler Pre-School and Primary Scale of Intelligence (3rd edn), visual attention, visuomotor precision, sentence repetition and verbal fluency measured by the NEPSY, and visual form-constancy measured by the Test of Visual-Perceptual Skills (Non-Motor). RESULTS: In unadjusted analyses, children for whom breast milk or DHA-fortified formula was the main method of feeding throughout the first 6 months of life had higher mean full-scale and verbal IQ scores at age 4 years than those fed mainly unfortified formula. After adjustment for potential confounding factors, particularly maternal IQ and educational attainment, the differences in IQ between children in the breast milk and unfortified formula groups were severely attenuated, but children who were fed DHA-fortified formula had full-scale and verbal IQ scores that were respectively 5.62 (0.98 to 10.2) and 7.02 (1.56 to 12.4) points higher than children fed unfortified formula. However, estimated total intake of DHA in milk up to age 6 months was not associated with subsequent IQ or with score on any other test. CONCLUSIONS: Differences in children's intelligence according to type of milk fed in infancy may be due more to confounding by maternal or family characteristics than to the amount of long-chain polyunsaturated fatty acids they receive in milk

Robo-AO M-dwarf Multiplicity Survey: Catalog

We analyze observations from Robo-AO's field M dwarf survey taken on the 2.1 m Kitt Peak telescope and perform a multiplicity comparison with Gaia DR2. Through its laser-guided, automated system, the Robo-AO instrument has yielded the largest adaptive optics M dwarf multiplicity survey to date. After developing an interface to visually identify and locate stellar companions, we selected 11 low-significance Robo-AO detections for follow-up on the Keck II telescope using NIRC2. In the Robo-AO survey we find 553 candidate companions within 4'' around 534 stars out of 5566 unique targets, most of which are new discoveries. Using a position cross-match with DR2 on all targets, we assess the binary recoverability of Gaia DR2 and compare the properties of multiples resolved by both Robo-AO and Gaia. The catalog of nearby M dwarf systems and their basic properties presented here can assist other surveys which observe these stars, such as the NASA TESS mission

Knowledge practices in design: The role of visual representations as 'epistemic objects'

We use a detailed study of the knowledge work around visual representations to draw attention to the multidimensional nature of `objects'. Objects are variously described in the literatures as relatively stable or in flux; as abstract or concrete; and as used within or across practices. We clarify these dimensions, drawing on and extending the literature on boundary objects, and connecting it with work on epistemic and technical objects. In particular, we highlight the epistemic role of objects, using our observations of knowledge work on an architectural design project to show how, in this setting, visual representations are characterized by a `lack' or incompleteness that precipitates unfolding. The conceptual design of a building involves a wide range of technical, social and aesthetic forms of knowledge that need to be developed and aligned. We explore how visual representations are used, and how these are meaningful to different stakeholders, eliciting their distinct contributions. As the project evolves and the drawings change, new issues and needs for knowledge work arise. These objects have an `unfolding ontology' and are constantly in flux, rather than fully formed. We discuss the implications for wider understandings of objects in organizations and for how knowledge work is achieved in practice

Know The Star, Know the Planet. IV. A Stellar Companion to the Host star of the Eccentric Exoplanet HD 8673b

HD 8673 hosts a massive exoplanet in a highly eccentric orbit (e=0.723). Based on two epochs of speckle interferometry a previous publication identified a candidate stellar companion. We observed HD 8673 multiple times with the 10 m Keck II telescope, the 5 m Hale telescope, the 3.63 m AEOS telescope and the 1.5m Palomar telescope in a variety of filters with the aim of confirming and characterizing the stellar companion. We did not detect the candidate companion, which we now conclude was a false detection, but we did detect a fainter companion. We collected astrometry and photometry of the companion on six epochs in a variety of filters. The measured differential photometry enabled us to determine that the companion is an early M dwarf with a mass estimate of 0.33-0.45 M?. The companion has a projected separation of 10 AU, which is one of the smallest projected separations of an exoplanet host binary system. Based on the limited astrometry collected, we are able to constrain the orbit of the stellar companion to a semi-major axis of 35{60 AU, an eccentricity ? 0.5 and an inclination of 75{85?. The stellar companion has likely strongly in uenced the orbit of the exoplanet and quite possibly explains its high eccentricity.Comment: Accepted to the Astronomical Journal, 6 Pages, 5 Figure

Discovery of a Dynamical Cold Point in the Heart of the Sagittarius dSph Galaxy with Observations from the APOGEE Project

The dynamics of the core of the Sagittarius (Sgr) dwarf spheroidal (dSph) galaxy are explored using high-resolution (R~22,500), H-band, near-infrared spectra of over 1,000 giant stars in the central 3 deg^2 of the system, of which 328 are identified as Sgr members. These data, among some of the earliest observations from the SDSS-III/Apache Point Observatory Galactic Evolution Experiment (APOGEE) and the largest published sample of high resolution Sgr dSph spectra to date, reveal a distinct gradient in the velocity dispersion of Sgr from 11-14 km/s for radii >0.8 degrees from center to a dynamical cold point of 8 km/s in the Sgr center --- a trend differing from that found in previous kinematical analyses of Sgr over larger scales that suggest a more or less flat dispersion profile at these radii. Well-fitting mass models with either cored and cusped dark matter distributions can be found to match the kinematical results, although the cored profile succeeds with significantly more isotropic stellar orbits than required for a cusped profile. It is unlikely that the cold point reflects an unusual mass distribution. The dispersion gradient may arise from variations in the mixture of populations with distinct kinematics within the dSph; this explanation is suggested (e.g., by detection of a metallicity gradient across similar radii), but not confirmed, by the present data. Despite these remaining uncertainties about their interpretation, these early test data (including some from instrument commissioning) demonstrate APOGEE's usefulness for precision dynamical studies, even for fields observed at extreme airmasses.Comment: 15 pages, 3 figure

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening

The E1 and E2 envelope proteins of hepatitis C virus (HCV) form a heterodimer that drives virus-host membrane fusion. Here, we analyze the role of each amino acid in E1E2 function, expressing 545 individual alanine mutants of E1E2 in human cells, incorporating them into infectious viral pseudoparticles, and testing them against 37 different monoclonal antibodies (MAbs) to ascertain full-length translation, folding, heterodimer assembly, CD81 binding, viral pseudoparticle incorporation, and infectivity. We propose a model describing the role of each critical residue in E1E2 functionality and use it to examine how MAbs neutralize infection by exploiting functionally critical sites of vulnerability on E1E2. Our results suggest that E1E2 is a surprisingly fragile protein complex where even a single alanine mutation at 92% of positions disrupts its function. The amino-acid-level targets identified are highly conserved and functionally critical and can be exploited for improved therapies and vaccines

Robo-AO M-dwarf Multiplicity Survey: Catalog

We analyze observations from Robo-AO's field M dwarf survey taken on the 2.1 m Kitt Peak telescope and perform a multiplicity comparison with Gaia DR2. Through its laser-guided, automated system, the Robo-AO instrument has yielded the largest adaptive optics M dwarf multiplicity survey to date. After developing an interface to visually identify and locate stellar companions, we selected 11 low-significance Robo-AO detections for follow-up on the Keck II telescope using NIRC2. In the Robo-AO survey we find 553 candidate companions within 4'' around 534 stars out of 5566 unique targets, most of which are new discoveries. Using a position cross-match with DR2 on all targets, we assess the binary recoverability of Gaia DR2 and compare the properties of multiples resolved by both Robo-AO and Gaia. The catalog of nearby M dwarf systems and their basic properties presented here can assist other surveys which observe these stars, such as the NASA TESS mission