Pharmacotherapies for Diabetic Retinopathy: Present and Future

Diabetic retinopathy remains a major cause of worldwide preventable blindness. Measures to avoid blindness include medical management (control of blood sugar, blood pressure, and serum lipids) and ocular management (laser photocoagulation and pars plana vitrectomy). Adjunctive pharmacologic therapies (intravitreal triamcinolone acetonide and anti-vascular endothelial growth factor agents) have shown early promise in the treatment of both diabetic macular edema and proliferative diabetic retinopathy. Other medications under investigation include the fluocinolone acetonide implantable device, extended-release dexamethasone implant, oral ruboxistaurin, and intravitreal hyaluronidase

Lipemia Retinalis, Macular Edema, and Vision Loss in a Diabetic Patient with a History of Type IV Hypertriglyceridemia and Pancreatitis

Background: Lipemia retinalis is a rare but known complication of elevated serum triglycerides. This case describes the clinical course of a diabetic patient who presented with lipemia retinalis and macular edema, which responded to systemic and local treatments. Case Report: A 40-year-old female with a history of type II diabetes mellitus, hypertriglyceridemia, and pancreatitis presented with decreased vision in the left eye. She had peripapillary and macular edema, intraretinal hemorrhages, and prominent exudates in the setting of lipemia retinalis due to type IV hypertriglyceridemia. She was treated with serial intravitreal bevacizumab injections for macular edema and systemic lipid lowering therapy, and her visual acuity improved back to baseline. Conclusions: In the setting of lipemia retinalis and hypertriglyceridemia, the current patient developed macular edema and vision loss. The macular edema was treated with intravitreal injections of bevacizumab, and the patient experienced a rapid recovery of visual acuity

Delayed-onset endophthalmitis associated with corneal suture infections

BACKGROUND: The purpose of the current study was to report the microbiology, risk factors, and treatment outcomes in patients with delayed-onset endophthalmitis associated with corneal suture infections. For this retrospective consecutive case series, a search of the ocular microbiology department database was performed to identify all patients with positive corneal and intraocular cultures (anterior chamber and/or vitreous) between 01 January 1995 and 01 January 2010. A subset of patients with a history of corneal suture infections and delayed-onset endophthalmitis was identified. RESULTS: Over the 15-year period of the study, 68 patients were identified to have both positive corneal and intraocular cultures. Among them, six patients were identified to have a culture-proven, delayed-onset endophthalmitis that developed from a culture-positive corneal suture infection. All of the patients in the current study were using topical corticosteroids at the time of diagnosis. In four of six patients, there was documented manipulation of a suture before the development of endophthalmitis. Streptoccocus was identified as the causative organism in five of six patients in the current study. All of the Streptoccocus isolates were sensitive to vancomycin. The single case of Serratia marcescens endophthalmitis was sensitive to amikacin, ceftazidime, ciprofloxacin, gentamicin, and tobramycin. Treatment modalities varied and were guided by the attending ophthalmologist depending upon clinical presentation. One patient with severe Streptococcus pyogenes keratitis and endophthalmitis underwent a primary enucleation after developing a wound dehiscence. Of the remaining five patients, all received topical and intravitreal antibiotics. Therapeutic penetrating keratoplasty was performed in three patients. Pars plana vitrectomy was performed in two patients. Visual acuity outcomes ranged from 20/150 to no light perception. CONCLUSIONS: In the current study, Streptococcus was isolated in nearly all patients with delayed-onset endophthalmitis associated with corneal suture infections. Topical steroid use and suture manipulation were identified as associated factors for developing endophthalmitis. Visual acuity outcomes were poor despite the prompt recognition of endophthalmitis and appropriate antibiotic therapy

Quantitative Serial MRI of the Treated Fibroid Uterus

There are no long-term medical treatments for uterine fibroids, and non-invasive biomarkers are needed to evaluate novel therapeutic interventions. The aim of this study was to determine whether serial dynamic contrast-enhanced MRI (DCE-MRI) and magnetization transfer MRI (MT-MRI) are able to detect changes that accompany volume reduction in patients administered GnRH analogue drugs, a treatment which is known to reduce fibroid volume and perfusion. Our secondary aim was to determine whether rapid suppression of ovarian activity by combining GnRH agonist and antagonist therapies results in faster volume reduction.Forty women were assessed for eligibility at gynaecology clinics in the region, of whom thirty premenopausal women scheduled for hysterectomy due to symptomatic fibroids were randomized to three groups, receiving (1) GnRH agonist (Goserelin), (2) GnRH agonist+GnRH antagonist (Goserelin and Cetrorelix) or (3) no treatment. Patients were monitored by serial structural, DCE-MRI and MT-MRI, as well as by ultrasound and serum oestradiol concentration measurements from enrolment to hysterectomy (approximately 3 months).A volumetric treatment effect assessed by structural MRI occurred by day 14 of treatment (9% median reduction versus 9% increase in untreated women; P = 0.022) and persisted throughout. Reduced fibroid perfusion and permeability assessed by DCE-MRI occurred later and was demonstrable by 2-3 months (43% median reduction versus 20% increase respectively; P = 0.0093). There was no apparent treatment effect by MT-MRI. Effective suppression of oestradiol was associated with early volume reduction at days 14 (P = 0.041) and 28 (P = 0.0061).DCE-MRI is sensitive to the vascular changes thought to accompany successful GnRH analogue treatment of uterine fibroids and should be considered for use in future mechanism/efficacy studies of proposed fibroid drug therapies. GnRH antagonist administration does not appear to accelerate volume reduction, though our data do support the role of oestradiol suppression in GnRH analogue treatment of fibroids.ClinicalTrials.gov NCT00746031

First measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary–Black-hole Merger GW170814

International audienceWe present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

GWTC-1: A Gravitational-Wave Transient Catalog of Compact Binary Mergers Observed by LIGO and Virgo during the First and Second Observing Runs

We present the results from three gravitational-wave searches for coalescing compact binaries with component masses above 1  M⊙ during the first and second observing runs of the advanced gravitational-wave detector network. During the first observing run (O1), from September 12, 2015 to January 19, 2016, gravitational waves from three binary black hole mergers were detected. The second observing run (O2), which ran from November 30, 2016 to August 25, 2017, saw the first detection of gravitational waves from a binary neutron star inspiral, in addition to the observation of gravitational waves from a total of seven binary black hole mergers, four of which we report here for the first time: GW170729, GW170809, GW170818, and GW170823. For all significant gravitational-wave events, we provide estimates of the source properties. The detected binary black holes have total masses between 18.6−0.7+3.2  M⊙ and 84.4−11.1+15.8  M⊙ and range in distance between 320−110+120 and 2840−1360+1400  Mpc. No neutron star-black hole mergers were detected. In addition to highly significant gravitational-wave events, we also provide a list of marginal event candidates with an estimated false-alarm rate less than 1 per 30 days. From these results over the first two observing runs, which include approximately one gravitational-wave detection per 15 days of data searched, we infer merger rates at the 90% confidence intervals of 110−3840  Gpc−3 y−1 for binary neutron stars and 9.7−101  Gpc−3 y−1 for binary black holes assuming fixed population distributions and determine a neutron star-black hole merger rate 90% upper limit of 610  Gpc−3 y−1

Erratum: “Searches for Gravitational Waves from Known Pulsars at Two Harmonics in 2015–2017 LIGO Data” (2019, ApJ, 879, 10)

Due to an error at the publisher, in the published article the number of pulsars presented in the paper is incorrect in multiple places throughout the text. Specifically, "222" pulsars should be "221." Additionally, the number of pulsars for which we have EM observations that fully overlap with O1 and O2 changes from "168" to "167." Elsewhere, in the machine-readable table of Table 1 and in Table 2, the row corresponding to pulsar J0952-0607 should be excised as well. Finally, in the caption for Table 2 the number of pulsars changes from "188" to "187.

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure