A dramatic, objective antiandrogen withdrawal response: case report and review of the literature

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation

The X-Ray Properties of the Optically Brightest Mini-BAL Quasars from the Sloan Digital Sky Survey

We have compiled a sample of 14 of the optically brightest radio-quiet quasars ($m_{i}$~$\le$~17.5 and $z$~$\ge$~1.9) in the Sloan Digital Sky Survey Data Release 5 quasar catalog that have C IV mini-BALs present in their spectra. X-ray data for 12 of the objects were obtained via a Chandra snapshot survey using ACIS-S, while data for the other two quasars were obtained from archival XMM-Newton observations. Joint X-ray spectral analysis shows the mini-BAL quasars have a similar average power-law photon index ($\Gamma\approx1.9$) and level of intrinsic absorption ($N_H \lesssim 8\times 10^{21} \ {\rm cm}^{-2}$) as non-BMB (neither BAL nor mini-BAL) quasars. Mini-BAL quasars are more similar to non-BMB quasars than to BAL quasars in their distribution of relative X-ray brightness (assessed with $\Delta\alpha_{\rm ox}$). Relative colors indicate mild dust reddening in the optical spectra of mini-BAL quasars. Significant correlations between $\Delta\alpha_{\rm ox}$ and UV absorption properties are confirmed for a sample of 56 sources combining mini-BAL and BAL quasars with high signal-to-noise ratio rest-frame UV spectra, which generally supports models in which X-ray absorption is important in enabling driving of the UV absorption-line wind. We also propose alternative parametrizations of the UV absorption properties of mini-BAL and BAL quasars, which may better describe the broad absorption troughs in some respects.Comment: ApJ accepted; 21 pages, 11 figures, and 9 table

A Rare Variant in ERF (rs144812092) Predisposes to Prostate and Bladder Cancers in an Extended Pedigree

Simple SummaryHere we applied a powerful predisposition candidate gene identification strategy to identify rare variants shared by two related bladder cancer cases who were members of pedigrees exhibiting a significant excess of bladder cancers. We sequenced the exomes of pairs of related bladder cancer cases belonging to high-risk bladder cancer pedigrees to identify rare, shared variants shared as candidates for predisposition. A rare, shared variant in ERF was also found to show significant association with bladder cancer risk in an independent population, was present in other prostate cancer-affected members in the pedigree, and showed evidence for altering the function of the associated protein. This evidence supports ERF (ETS2 Repressor Factor) as a bladder and prostate cancer predisposition gene.Pairs of related bladder cancer cases who belong to pedigrees with an excess of bladder cancer were sequenced to identify rare, shared variants as candidate predisposition variants. Candidate variants were tested for association with bladder cancer risk. A validated variant was assayed for segregation to other related cancer cases, and the predicted protein structure of this variant was analyzed. This study of affected bladder cancer relative pairs from high-risk pedigrees identified 152 bladder cancer predisposition candidate variants. One variant in ERF (ETS Repressing Factor) was significantly associated with bladder cancer risk in an independent population, was observed to segregate with bladder and prostate cancer in relatives, and showed evidence for altering the function of the associated protein. This finding of a rare variant in ERF that is strongly associated with bladder and prostate cancer risk in an extended pedigree both validates ERF as a cancer predisposition gene and shows the continuing value of analyzing affected members of high-risk pedigrees to identify and validate rare cancer predisposition variants

High-Redshift SDSS Quasars with Weak Emission Lines

We identify a sample of 74 high-redshift quasars (z>3) with weak emission lines from the Fifth Data Release of the Sloan Digital Sky Survey and present infrared, optical, and radio observations of a subsample of four objects at z>4. These weak emission-line quasars (WLQs) constitute a prominent tail of the Lya+NV equivalent width distribution, and we compare them to quasars with more typical emission-line properties and to low-redshift active galactic nuclei with weak/absent emission lines, namely BL Lac objects. We find that WLQs exhibit hot (T~1000 K) thermal dust emission and have rest-frame 0.1-5 micron spectral energy distributions that are quite similar to those of normal quasars. The variability, polarization, and radio properties of WLQs are also different from those of BL Lacs, making continuum boosting by a relativistic jet an unlikely physical interpretation. The most probable scenario for WLQs involves broad-line region properties that are physically distinct from those of normal quasars.Comment: Updated to match version published in ApJ. 20 pages, 12 figure

A Quasar Catalog with Simultaneous UV, Optical and X-ray Observations by Swift

We have compiled a catalog of optically-selected quasars with simultaneous observations in UV/optical and X-ray bands by the Swift Gamma Ray Burst Explorer. Objects in this catalog are identified by matching the Swift pointings with the Sloan Digital Sky Survey Data Release 5 quasar catalog. The final catalog contains 843 objects, among which 637 have both UVOT and XRT observations and 354 of which are detected by both instruments. The overall X-ray detection rate is ~60% which rises to ~85% among sources with at least 10 ks of XRT exposure time. We construct the time-averaged spectral energy distribution for each of the 354 quasars using UVOT photometric measurements and XRT spectra. From model fits to these SEDs, we find that the big blue bump contributes about 0.3 dex to the quasar luminosity. We re-visit the alpha_ox-L_uv relation by selecting a clean sample with only type 1 radio-quiet quasars; the dispersion of this relation is reduced by at least 15% compared to studies that use non-simultaneous UV/optical and X-ray data. We only found a weak correlation between L/L_Edd and alpha_uv. We do not find significant correlations between alpha_x and alpha_ox, alpha_ox and alpha_uv, and alpha_x and Log L(0.3-10 keV). The correlations between alpha_uv and alpha_x, alpha_ox and alpha_x, alpha_ox and alpha_uv, L/L_Edd and alpha_x, and L/L_Edd and alpha_ox are stronger amongst low-redshift quasars, indicating that these correlations are likely driven by the changes of SED shape with accretion state.Comment: 63 pages, 22 figures, accepted by ApJ

Eight-Dimensional Mid-Infrared/Optical Bayesian Quasar Selection

We explore the multidimensional, multiwavelength selection of quasars from mid-IR (MIR) plus optical data, specifically from Spitzer-IRAC and the Sloan Digital Sky Survey (SDSS). We apply modern statistical techniques to combined Spitzer MIR and SDSS optical data, allowing up to 8-D color selection of quasars. Using a Bayesian selection method, we catalog 5546 quasar candidates to an 8.0 um depth of 56 uJy over an area of ~24 sq. deg; ~70% of these candidates are not identified by applying the same Bayesian algorithm to 4-color SDSS optical data alone. Our selection recovers 97.7% of known type 1 quasars in this area and greatly improves the effectiveness of identifying 3.5<z<5 quasars. Even using only the two shortest wavelength IRAC bandpasses, it is possible to use our Bayesian techniques to select quasars with 97% completeness and as little as 10% contamination. This sample has a photometric redshift accuracy of 93.6% (Delta Z +/-0.3), remaining roughly constant when the two reddest MIR bands are excluded. While our methods are designed to find type 1 (unobscured) quasars, as many as 1200 of the objects are type 2 (obscured) quasar candidates. Coupling deep optical imaging data with deep mid-IR data could enable selection of quasars in significant numbers past the peak of the quasar luminosity function (QLF) to at least z~4. Such a sample would constrain the shape of the QLF and enable quasar clustering studies over the largest range of redshift and luminosity to date, yielding significant gains in our understanding of quasars and the evolution of galaxies.Comment: 49 pages, 14 figures, 7 tables. AJ, accepte

Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium: Vitamin D SNPs and Breast Cancer Risk in African American Women

Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER− breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER− cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10−5, gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10−4, corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes

Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses.In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women