An Analysis of the Effect of ABCA4 p.Asn1868Ile Genotypes on Retinal Structure in 26,558 Participants in the UK Biobank

PURPOSE: To determine whether the ABCA4 retinopathy-associated variant p.Asn1868Ile (c.5603A>T) is associated with retinal structure or subclinical disease among the general population. METHODS: UK Biobank participants of European ancestry with available spectral-domain optical coherence tomography (OCT) passing quality control metrics and exome sequencing data were included. Regression analyses using both linear and recessive models tested for the association between the p.Asn1868Ile variant and total retinal thickness, clinically relevant segmented layer thicknesses, and visual acuity. Further regression analyses were performed with automated quality control metrics to determine if the p.Asn1868Ile variant is associated with poor quality or abnormal scans. RESULTS: Retinal layer segmentation and sequencing data for the p.Asn1868Ile variant were available for 26,558 participants, following exclusions. We identified no significant association between the p.Asn1868Ile variant and retinal thickness, any of the segmented layers, or visual acuity. There was also no significant difference for homozygous p.Asn1868Ile when tested under the assumption of a recessive model. No association was identified for any of the quality control metrics, and a χ2 test showed that participants with the p.Asn1868Ile variant were not more likely to be excluded during quality control due to poor quality scans (P = 0.56). CONCLUSIONS: The p.Asn1868Ile variant does not appear to affect the retinal structure or have pathogenic or subclinical effects on its own within the general population. The variant is likely to require other specific cis- or trans-acting modifying factors to cause ABCA4 retinopathy

SPIRITS 15c and SPIRITS 14buu: Two Obscured Supernovae in the Nearby Star-Forming Galaxy IC 2163

SPIRITS---SPitzer InfraRed Intensive Transients Survey---is an ongoing survey of nearby galaxies searching for infrared (IR) transients with Spitzer/IRAC. We present the discovery and follow-up observations of one of our most luminous ($M_{[4.5]} = -17.1\pm0.4$ mag, Vega) and red ($[3.6] - [4.5] = 3.0 \pm 0.2$ mag) transients, SPIRITS 15c. The transient was detected in a dusty spiral arm of IC 2163 ($D\approx35.5$ Mpc). Pre-discovery ground-based imaging revealed an associated, shorter-duration transient in the optical and near-IR (NIR). NIR spectroscopy showed a broad ($\approx 8400$ km s$^{-1}$), double-peaked emission line of He I at $1.083 \mu$m, indicating an explosive origin. The NIR spectrum of SPIRITS 15c is similar to that of the Type IIb SN 2011dh at a phase of $\approx 200$ days. Assuming $A_V = 2.2$ mag of extinction in SPIRITS 15c provides a good match between their optical light curves. The IR light curves and the extreme $[3.6]-[4.5]$ color cannot be explained using only a standard extinction law. Another luminous ($M_{4.5} = -16.1\pm0.4$ mag) event, SPIRITS 14buu, was serendipitously discovered in the same galaxy. The source displays an optical plateau lasting $\gtrsim 80$ days, and we suggest a scenario similar to the low-luminosity Type IIP SN 2005cs obscured by $A_V \approx 1.5$ mag. Other classes of IR-luminous transients can likely be ruled out in both cases. If both events are indeed SNe, this may suggest $\gtrsim 18\%$ of nearby core-collapse SNe are missed by currently operating optical surveys.Comment: 19 pages, 7 Figures, 4 Table

Clouds in the Coldest Brown Dwarfs: FIRE Spectroscopy of Ross 458C

Condensate clouds are a salient feature of L dwarf atmospheres, but have been assumed to play little role in shaping the spectra of the coldest T-type brown dwarfs. Here we report evidence of condensate opacity in the near-infrared spectrum of the brown dwarf candidate Ross 458C, obtained with the Folded-Port Infrared Echellette (FIRE) spectrograph at the Magellan Telescopes. These data verify the low-temperature nature of this source, indicating a T8 spectral classification, log Lbol/Lsun = -5.62+/-0.03, Teff = 650+/-25 K, and a mass at or below the deuterium burning limit. The data also reveal enhanced emission at K-band associated with youth (low surface gravity) and supersolar metallicity, reflecting the properties of the Ross 458 system (age = 150-800 Myr, [Fe/H] = +0.2 to +0.3). We present fits of FIRE data for Ross 458C, the T9 dwarf ULAS J133553.45+113005.2, and the blue T7.5 dwarf SDSS J141624.08+134826.7B, to cloudless and cloudy spectral models from Saumon & Marley. For Ross 458C we confirm a low surface gravity and supersolar metallicity, while the temperature differs depending on the presence (635 [+25,-35] K) or absence (760 [+70,-45] K) of cloud extinction. ULAS J1335+1130 and SDSS J1416+1348B have similar temperatures (595 [+25,-45] K), but distinct surface gravities (log g = 4.0-4.5 cgs versus 5.0-5.5 cgs) and metallicities ([M/H] ~ +0.2 versus -0.2). In all three cases, cloudy models provide better fits to the spectral data, significantly so for Ross 458C. These results indicate that clouds are an important opacity source in the spectra of young cold T dwarfs, and should be considered when characterizing the spectra of planetary-mass objects in young clusters and directly-imaged exoplanets. The characteristics of Ross 458C suggest it could itself be regarded as a planet, albeit one whose cosmogony does not conform with current planet formation theories.Comment: Accepted for publication to ApJ: 18 pages, 11 figures in emulateapj forma

The Discovery of Y Dwarfs Using Data from the Wide-field Infrared Survey Explorer (WISE)

We present the discovery of seven ultracool brown dwarfs identified with the Wide-field Infrared Survey Explorer (WISE). Near-infrared spectroscopy reveals deep absorption bands of H_2O and CH_4 that indicate all seven of the brown dwarfs have spectral types later than UGPS J072227.51-054031.2, the latest type T dwarf currently known. The spectrum of WISEP J182831.08+265037.8 is distinct in that the heights of the J- and H-band peaks are approximately equal in units of f_lambda, so we identify it as the archetypal member of the Y spectral class. The spectra of at least two of the other brown dwarfs exhibit absorption on the blue wing of the H-band peak that we tentatively ascribe to NH_3. These spectral morphological changes provide a clear transition between the T dwarfs and the Y dwarfs. In order to produce a smooth near-infrared spectral sequence across the T/Y dwarf transition, we have reclassified UGPS J0722-0540 as the T9 spectral standard and tentatively assign WISEP J173835.52+273258.9 as the Y0 spectral standard. In total, six of the seven new brown dwarfs are classified as Y dwarfs: four are classified as Y0, one is classified as Y0 (pec?), and WISEP J1828+2650 is classified as >Y0. We have also compared the spectra to the model atmospheres of Marley and Saumon and infer that the brown dwarfs have effective temperatures ranging from 300 K to 500 K, making them the coldest spectroscopically confirmed brown dwarfs known to date.Comment: Submitted June 11 and accepted August 2 for publication in the Astrophysical Journa

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size

Preserving the Royalty-Free Standards Ecosystem

It has long been recognized in Europe and elsewhere that standards-development organizations (SDOs) may adopt policies that require their participants to license patents essential to the SDO’s standards (standards-essential patents or SEPs) to manufacturers of standardized products (“implementers”) on a royalty-free (RF) basis.1 This requirement contrasts with SDO policies that permit SEP holders to charge implementers monetary patent royalties, sometimes on terms that are specified as “fair, reasonable and nondiscriminatory” (FRAND). As demonstrated by two decades of intensive litigation around the world, FRAND royalties have given rise to intractable disputes regarding the manner in which such royalties should be calculated and adjudicated. In contrast, standards distributed on an RF basis are comparatively free from litigation and the attendant transaction costs.2 Accordingly, numerous SDOs around the world have adopted RF licensing policies and many widely adopted standards, including Bluetooth, USB, IPv6, HTTP, HTML and XML, are distributed on an RF basis. This note briefly discusses the commercial considerations surrounding RF standards, the relationship between RF standards and open source software (OSS) and the SDO policy mechanisms – including “universal reciprocity” -- that enable RF licensing to succeed in the marketplace

Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia.

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future

PTF10iya: A short-lived, luminous flare from the nuclear region of a star-forming galaxy

We present the discovery and characterisation of PTF10iya, a short-lived (dt ~ 10 d, with an optical decay rate of ~ 0.3 mag per d), luminous (M_g ~ -21 mag) transient source found by the Palomar Transient Factory. The ultraviolet/optical spectral energy distribution is reasonably well fit by a blackbody with T ~ 1-2 x 10^4 K and peak bolometric luminosity L_BB ~ 1-5 x 10^44 erg per s (depending on the details of the extinction correction). A comparable amount of energy is radiated in the X-ray band that appears to result from a distinct physical process. The location of PTF10iya is consistent with the nucleus of a star-forming galaxy (z = 0.22405 +/- 0.00006) to within 350 mas (99.7 per cent confidence radius), or a projected distance of less than 1.2 kpc. At first glance, these properties appear reminiscent of the characteristic "big blue bump" seen in the near-ultraviolet spectra of many active galactic nuclei (AGNs). However, emission-line diagnostics of the host galaxy, along with a historical light curve extending back to 2007, show no evidence for AGN-like activity. We therefore consider whether the tidal disruption of a star by an otherwise quiescent supermassive black hole may account for our observations. Though with limited temporal information, PTF10iya appears broadly consistent with the predictions for the early "super-Eddington" phase of a solar-type star disrupted by a ~ 10^7 M_sun black hole. Regardless of the precise physical origin of the accreting material, the large luminosity and short duration suggest that otherwise quiescent galaxies can transition extremely rapidly to radiate near the Eddington limit; many such outbursts may have been missed by previous surveys lacking sufficient cadence.Comment: 18 pages, 8 figures; revised following referee's comment