Association of Disease Location and Treatment With Survival in Diffuse Large B-Cell Lymphoma of the Eye and Ocular Adnexal Region.

Importance: Primary diffuse large B-cell lymphoma (DLBCL) of the ocular region is rare, and the utility of surgery and radiation therapy remains unresolved. Objective: To explore the clinical characteristics and determine factors associated with overall survival in primary vitreoretinal lymphoma (PVRL) and ocular adnexal (OA)-uveal DLBCL. Design, Setting, and Participants: This retrospective analysis included 396 patients with ophthalmic DLBCL from January 1, 1973, through December 31, 2014, using the Surveillance, Epidemiology, and End Results database. The median follow-up was 39.0 months (interquartile range, 5.1-72.9 months). All patients diagnosed with primary DLBCL of the eye or retina (PVRL) or the eyelid, conjunctiva, choroid, ciliary body, lacrimal gland, or orbit (OA-uveal lymphoma) were included. Patients diagnosed at autopsy or with additional neoplastic disease were excluded. Main Outcomes and Measures: Patient demographic characteristics, disease location, treatment modalities, and overall survival. Results: Forty-seven patients with PVRL (24 women [51.1%] and 23 men [48.9%]) and 349 with OA-uveal DLBCL (192 women [55.0%] and 157 men [45.0%]) had a similar mean (SD) age at diagnosis (69.6 [12.3] vs 66.1 [17.7] years). No difference in the use of surgery or radiation therapy by location was found. For all PVRL and OA-uveal DLBCL, a Cox proportional hazards regression model affirmed that age older than 60 years was associated with increased risk for death (hazard ratio [HR], 2.7; 95% CI, 1.9-4.0; P \u3c .001). Gross total resection was associated with a decreased risk for death (HR, 0.5; 95% CI, 0.3-0.9; P = .04), whereas radiation therapy was not. The 5-year overall survival among patients with PVRL was 41.4% (SE, 8.6%); among those with OA-uveal DLBCL, 59.1% (SE, 2.8%; Mantel-Cox test, P = .007). Median overall survival was lower in PVRL (38.0 months; 95% CI, 14.2-61.8 months) than in OA-uveal DLBCL (96.0 months; 95% CI, 67.3-124.7 months; Mantel-Cox test, P = .007). In addition, median overall survival in ophthalmic-only disease was higher (84.0 months; 95% CI, 63.2-104.8 months) than that in primary DLBCL that occurred outside the central nervous system and ophthalmic regions (46.0 months; 95% CI, 44.4-47.6 months; Mantel-Cox test, P \u3c .001). Conclusions and Relevance: The 5-year survival in PVRL vs OA-uveal DLBCL differed by 17.7%, and overall survival was greater in ophthalmic DLBCL than in DLBCL located outside the central nervous system and ophthalmic regions. Younger age (≤60 years) and gross total resection were associated with increased survival

Emission-Line Properties of z > 4 Quasars

We present results of a program of high signal-to-noise spectroscopy for 44 QSOs at redshifts > 4 using the MMT and Keck observatories. The quasar spectra cover 1100 -- 1700 A in the rest frame for sources spanning a luminosity range of approximately 2 orders of magnitude. Comparisons between these data and spectra of lower redshift quasars reveal a high degree of similarity, although differences are present in the profiles and the strengths of some emission features. An examination of the luminosity dependence of the emission lines reveals evidence for a weak or absent Baldwin effect among z > 4 QSOs. We compare measurements for objects in our sample with results from other high redshift surveys characterized by different selection techniques. Distributions of equivalent widths for these different ensembles are consistent with a common parent population, suggesting that our sample is not strongly biased, or in any case, subject to selection effects that are not significantly different from other surveys, including the Sloan Digital Sky Survey. Based on this comparison, we tentatively conclude that the trends identified here are representative of high z QSOs. In particular, the data bolster indications of supersolar metallicities in these luminous, high-z sources, which support scenarios that assume substantial star formation at epochs preceding or concurrent with the QSO phenomena.Comment: 26 pages (incl. 9 figures), AASTeX v5.0, to appear in The Astrophysical Journa

Quasar outflow energetics from broad absorption line variability

Quasar outflows have long been recognized as potential contributors to the co-evolution between supermassive black holes (SMBHs) and their host galaxies. The role of outflows in AGN feedback processes can be better understood by placing observational constraints on wind locations and kinetic energies. We utilize broad absorption line (BAL) variability to investigate the properties of a sample of 71 BAL quasars with P$\thinspace$V broad absorption. The presence of P$\thinspace$V BALs indicates that other BALs like C$\thinspace$IV are saturated, such that variability in those lines favours clouds crossing the line of sight. We use these constraints with measurements of BAL variability to estimate outflow locations and energetics. Our data set consists of multiple-epoch spectra from the Sloan Digital Sky Survey and MDM Observatory. We detect significant (4$\sigma$) BAL variations from 10 quasars in our sample over rest frame time-scales between < 0.2-3.8 yr. Our derived distances for the 10 variable outflows are nominally < 1-10 pc from the SMBH using the transverse-motion scenario, and < 100-1000 pc from the central source using ionization-change considerations. These distances, in combination with the estimated high outflow column densities (i.e. $N_{\textrm{H}}$ > 10$^{22}$ cm$^{-2}$), yield outflow kinetic luminosities between ~ 0.001-1 times the bolometric luminosity of the quasar, indicating that many absorber energies within our sample are viable for AGN feedback.Comment: 19 pages, 3 figures, 4 tables, 1 supplementary figure, accepted to MNRA

The Extraordinary Abundances of QSO Broad Absorption Line Regions: A Matter of Novae?

The broad absorption lines (BALs) of QSOs indicate abundances of heavy elements, relative to hydrogen, that are 1 to 2 orders of magnitude higher than the solar values. In at least one QSO, an especially large enhancement of phosphorus is observed. These abundances resemble those in Galactic novae, and this suggests that novae may produce the BAL gas. The needed rate of nova outbursts may come from single white dwarfs that accrete gas as they pass through a supermassive accretion disk around a central black hole.Comment: 9 pages including 1 Postscript figure. Uses aaspp4.sty and flushrt.sty. Uuencoded, gzipped tarfile. To appear in Astrophys. J. (Letters), 1996 April 1

Identifying teeth and tooth fragments from digital 3D models

Dental anatomy is an essential skill for human identification in forensic odontology. With the advent of technology enabling virtual autopsies, there is scope for virtual consultation by forensic odontologists especially when the expertise is unavailable but needed in zones of conflict or disasters. This study aimed to investigate potential benefits and challenges of identifying intact and damaged teeth from 3D scanned digital models. Ten 3D tooth models – nine permanent and deciduous human teeth and one animal tooth were uploaded on a hosting platform. A 3-part survey was circulated among 60 forensic odontologists with questions about demography (P1), tooth identification of the scanned 3D models (P2) and the perceived usefulness of 3D models for tooth identification (P3). This was the first time that a survey required the identification of individual human teeth (intact or not) and animal tooth combined. The response rate for study participation was 58%. Substantial agreement among participants was seen in the determination of tooth classification (i.e., molars, premolars) or non-human and tooth within the same tooth class (i.e., lateral incisors, second molar) (both k=0.61). The least agreement (k=0.21) was seen in identification of tooth according to the FDI notation with a mean accuracy of 0.34. While most responders correctly identified the animal tooth, most incorrect responses were seen in the identifica-tion of the intact third molar. While 3D-scanned teeth have the potential to be identified virtually, fo-rensic odontologists should continuously test their skills in tooth morphology and dental anatomy of humans (damaged or not) and animals

Gigahertz quantum key distribution with InGaAs avalanche photodiodes

We report a demonstration of quantum key distribution (QKD) at GHz clock rates with InGaAs avalanche photodiodes (APDs) operating in a self-differencing mode. Such a mode of operation allows detection of extremely weak avalanches so that the detector afterpulse noise is sufficiently suppressed. The system is characterized by a secure bit rate of 2.37 Mbps at 5.6 km and 27.9 kbps at 65.5 km when the fiber dispersion is not compensated. After compensating the fiber dispersion, the QKD distance is extended to 101 km, resulting in a secure key rate of 2.88 kbps. Our results suggest that InGaAs APDs are very well suited to GHz QKD applications.Comment: 4 pages, 4 figure

Identifying teeth and tooth fragments from digital 3D models

Dental anatomy is an essential skill for human identification in forensic odontology. With the advent of technology enabling virtual autopsies, there is scope for virtual consultation by forensic odontologists especially when the expertise is unavailable but needed in zones of conflict or disasters. This study aimed to investigate potential benefits and challenges of identifying intact and damaged teeth from 3D scanned digital models. Ten 3D tooth models – nine permanent and deciduous human teeth and one animal tooth were uploaded on a hosting platform. A 3-part survey was circulated among 60 forensic odontologists with questions about demography (P1), tooth identification of the scanned 3D models (P2) and the perceived usefulness of 3D models for tooth identification (P3). This was the first time that a survey required the identification of individual human teeth (intact or not) and animal tooth combined. The response rate for study participation was 58%. Substantial agreement among participants was seen in the determination of tooth classification (i.e., molars, premolars) or non-human and tooth within the same tooth class (i.e., lateral incisors, second molar) (both k=0.61). The least agreement (k=0.21) was seen in identification of tooth according to the FDI notation with a mean accuracy of 0.34. While most responders correctly identified the animal tooth, most incorrect responses were seen in the identifica-tion of the intact third molar. While 3D-scanned teeth have the potential to be identified virtually, fo-rensic odontologists should continuously test their skills in tooth morphology and dental anatomy of humans (damaged or not) and animals

Ultraviolet and optical properties of Narrow-Line Seyfert 1 galaxies

Narrow Line Seyfert 1 (NLS1) galaxies are remarkable for their extreme continuum and emission line properties which are not well understood. New results bearing on the spectroscopic characteristics of these objects are presented here, with the aim of establishing their typical ultraviolet and optical spectral behavior. We employ HST observations of 22 NLS1s, which represent a substantial improvement over previous work in terms of data quality and sample size. High signal-to-noise NLS1 composite spectra are constructed, allowing accurate measurements of the continuum shape and the strengths, ratios, and widths for lines, including weak features which are barely identifiable in other Active Galactic Nuclei (AGN) composites. We find that the NLS1 sources have redder UV-blue continua than those typically measured in other quasars and Seyferts. Objects with UV line absorption show redder spectra, suggesting that dust is important in modifying the continuum shapes. The data also permit a detailed investigation of the previously proposed link between NLS1s and z >~ 4 quasars. Direct comparison of their composite spectra, as well as a Principal Component Analysis, suggest that high-z QSOs do not show a strong preference toward NLS1 behavior.Comment: 23 pages (incl. 9 figures, 4 tables), to appear in The Publications of the Astronomical Society of the Pacifi

MicroRNA-125b transforms myeloid cell lines by repressing multiple mRNA

Background: We previously described a t(2;11)(p21;q23) chromosomal translocation found in patients with myelodysplasia or acute myeloid leukemia that leads to over-expression of the microRNA miR-125b, and we showed that transplantation of mice with murine stem/progenitor cells overexpressing miR-125b is able to induce leukemia. In this study, we investigated the mechanism of myeloid transformation by miR-125b. Design and Methods: To investigate the consequences of miR-125b over-expression on myeloid differentiation, apoptosis and proliferation, we used the NB4 and HL60 human promyelocytic cell lines and the 32Dclone3 murine promyelocytic cell line. To test whether miR-125b is able to transform myeloid cells, we used the non-tumorigenic and interleukin-3-dependent 32Dclone3 cell line over-expressing miR-125b, in xenograft experiments in nude mice and in conditions of interleukin-3 deprivation. To identify new miR-125b targets, we compared, by RNA-sequencing, the transcriptome of cell lines that do or do not over-express miR-125b. Results: We showed that miR-125b over-expression blocks apoptosis and myeloid differentiation and enhances proliferation in both species. More importantly, we demonstrated that miR-125b is able to transform the 32Dclone3 cell line by conferring growth independence from interleukin-3; xenograft experiments showed that these cells form tumors in nude mice. Using RNA-sequencing and quantitative real-time polymerase chain reaction experiments, we identified multiple miR-125b targets. We demonstrated that ABTB1, an anti-proliferative factor, is a new direct target of miR-125b and we confirmed that CBFB, a transcription factor involved in hematopoiesis, is also targeted by miR-125b. MiR-125b controls apoptosis by down-regulating genes involved in the p53 pathway including BAK1 and TP53INP1. Conclusions: This study demonstrates that in a myeloid context, miR-125b is an oncomiR able to transform cell lines. miR-125b blocks myeloid differentiation in part by targeting CBFB, blocks apoptosis through down-regulation of multiple genes involved in the p53 pathway, and confers a proliferative advantage to human and mouse myeloid cell lines in part by targeting ABTB1.Leukemia & Lymphoma Society of AmericaNational Institutes of Health (U.S.) (NIH grant DK068348)National Institutes of Health (U.S.) (NIH grant 5P01 HL066105