Is Pregnancy-Associated Melanoma Associated with Adverse Outcomes?

BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in the media and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications. STUDY DESIGN: Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database. Clinical and histopathologic factors were analyzed with appropriate statistical methods. Univariable and then multivariable analysis were used on matched data to compare disease-free survival (DFS), overall survival (OS), and melanoma-specific survival (MSS) for stage 0-III PAMs vs non-PAMs. Kaplan-Meier survival curves were then plotted for OS and MSS and compared using the log-rank test. RESULTS: The clinical presentation of melanoma was similar for PAM and non-PAM patients. There was no significant difference in recurrence between the 2 groups; for PAM patients, 38.5% of patients had recurrence, as compared with 36.6% of non-PAM patients (p = 0.641). For PAM patients, median follow-up was 14.6 years (range 0 to 42.6 years) and 11.1 years (0 to 48.5 years) for the non-PAM patients. No significant differences in DFS, MSS, or OS were identified on univariable or multivariable analysis for PAM vs non-PAM patients in stage 0/I/II and stage III cutaneous melanoma, respectively (p = 0.880 DFS, p = 0.219 OS, and p = 0.670 MSS). CONCLUSIONS: We observed no difference in DFS, OS, or MSS between the 2 groups. Pregnant patients should be screened for melanoma in a similar manner to nonpregnant patients and should be counseled that their survival is not adversely affected by their pregnancy

CO J=2-1 line emission in cluster galaxies at z~1: fueling star formation in dense environments

We present observations of CO J=2-1 line emission in infrared-luminous cluster galaxies at z~1 using the IRAM Plateau de Bure Interferometer. Our two primary targets are optically faint, dust-obscured galaxies (DOGs) found to lie within 2 Mpc of the centers of two massive (>10^14 Msun) galaxy clusters. CO line emission is not detected in either DOG. We calculate 3-sigma upper limits to the CO J=2-1 line luminosities, L'_CO < 6.08x10^9 and < 6.63x10^9 K km/s pc^2. Assuming a CO-to-H_2 conversion factor derived for ultraluminous infrared galaxies in the local Universe, this translates to limits on the cold molecular gas mass of M_H_2 < 4.86x10^9 Msun and M_H_2 < 5.30x10^9 Msun. Both DOGs exhibit mid-infrared continuum emission that follows a power-law, suggesting that an AGN contributes to the dust heating. As such, estimates of the star formation efficiencies in these DOGs are uncertain. A third cluster member with an infrared luminosity, L_IR < 7.4x10^11 Lsun, is serendipitously detected in CO J=2-1 line emission in the field of one of the DOGs located roughly two virial radii away from the cluster center. The optical spectrum of this object suggests that it is likely an obscured AGN, and the measured CO line luminosity is L'_CO = (1.94 +/- 0.35)x10^10 K km/s pc^2, which leads to an estimated cold molecular gas mass M_H_2 = (1.55+/-0.28)x10^10 Msun. A significant reservoir of molecular gas in a z~1 galaxy located away from the cluster center demonstrates that the fuel can exist to drive an increase in star-formation and AGN activity at the outskirts of high-redshift clusters.Comment: 22 pages, 4 figures; accepted for publication in Ap

Star Formation and AGN Activity in Galaxy Clusters from z=1−2z=1-2: a Multi-wavelength Analysis Featuring HerschelHerschel/PACS

We present a detailed, multi-wavelength study of star formation (SF) and AGN activity in 11 near-infrared (IR) selected, spectroscopically confirmed, massive ($\gtrsim10^{14}\,\rm{M_{\odot}}$) galaxy clusters at $1<z<1.75$. Using new, deep $Herschel$/PACS imaging, we characterize the optical to far-IR spectral energy distributions (SEDs) for IR-luminous cluster galaxies, finding that they can, on average, be well described by field galaxy templates. Identification and decomposition of AGN through SED fittings allows us to include the contribution to cluster SF from AGN host galaxies. We quantify the star-forming fraction, dust-obscured SF rates (SFRs), and specific-SFRs for cluster galaxies as a function of cluster-centric radius and redshift. In good agreement with previous studies, we find that SF in cluster galaxies at $z\gtrsim1.4$ is largely consistent with field galaxies at similar epochs, indicating an era before significant quenching in the cluster cores ($r<0.5\,$Mpc). This is followed by a transition to lower SF activity as environmental quenching dominates by $z\sim1$. Enhanced SFRs are found in lower mass ($10.1< \log \rm{M_{\star}}/\rm{M_{\odot}}<10.8$) cluster galaxies. We find significant variation in SF from cluster-to-cluster within our uniformly selected sample, indicating that caution should be taken when evaluating individual clusters. We examine AGN in clusters from $z=0.5-2$, finding an excess AGN fraction at $z\gtrsim1$, suggesting environmental triggering of AGN during this epoch. We argue that our results $-$ a transition from field-like to quenched SF, enhanced SF in lower mass galaxies in the cluster cores, and excess AGN $-$ are consistent with a co-evolution between SF and AGN in clusters and an increased merger rate in massive haloes at high redshift.Comment: 26 pages, 14 figures, 6 tables with appendix, accepted for publication in the Astrophysical Journa

Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients.

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and AJCC stage III patients that are sentinel lymph node (SLN) positive receiving no immunotherapy (control cohort; n = 80). The SNP panel analysis demonstrated that the responder patient group had an improved disease-free survival (DFS) (hazard ratio [HR] 1.84, 95% CI 1.09-3.13, p = 0.021) in the pilot cohort. In the verification cohort, an improved overall survival (OS) (HR 1.67, 95% CI 1.07-2.67, p = 0.025) was observed. No significant differences of SNPs were observed in DFS or OS in the control patient cohort. This study demonstrates that SNP immune genes can be utilized as a predictive tool for identifying melanoma patients that are inherently responsive to BCG and potentially other immunotherapies in the future

Detecting the Most Distant (z>7) Objects with ALMA

Detecting and studying objects at the highest redshifts, out to the end of Cosmic Reionization at z>7, is clearly a key science goal of ALMA. ALMA will in principle be able to detect objects in this redshift range both from high-J (J>7) CO transitions and emission from ionized carbon, [CII], which is one of the main cooling lines of the ISM. ALMA will even be able to resolve this emission for individual targets, which will be one of the few ways to determine dynamical masses for systems in the Epoch of Reionization. We discuss some of the current problems regarding the detection and characterization of objects at high redshifts and how ALMA will eliminate most (but not all) of them.Comment: to appear in Astrophysics and Space Science, "Science with ALMA: a new era for Astrophysics", ed. R. Bachille

A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients.

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients\u27 disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients\u27 responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients\u27 and 73 normal donors\u27 plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors\u27 plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII

Far-IR/Submillimeter Spectroscopic Cosmological Surveys: Predictions of Infrared Line Luminosity Functions for z<4 Galaxies

Star formation and accretion onto supermassive black holes in the nuclei of galaxies are the two most energetic processes in the Universe, producing the bulk of the observed emission throughout its history. We simulated the luminosity functions of star-forming and active galaxies for spectral lines that are thought to be good spectroscopic tracers of either phenomenon, as a function of redshift. We focused on the infrared (IR) and sub-millimeter domains, where the effects of dust obscuration are minimal. Using three different and independent theoretical models for galaxy formation and evolution, constrained by multi-wavelength luminosity functions, we computed the number of star-forming and active galaxies per IR luminosity and redshift bin. We converted the continuum luminosity counts into spectral line counts using relationships that we calibrated on mid- and far-IR spectroscopic surveys of galaxies in the local universe. Our results demonstrate that future facilities optimized for survey-mode observations, i.e., the Space Infrared Telescope for Cosmology and Astrophysics (SPICA) and the Cerro Chajnantor Atacama Telescope (CCAT), will be able to observe thousands of z>1 galaxies in key fine-structure lines, e.g., [SiII], [OI], [OIII], [CII], in a half-square-degree survey, with one hour integration time per field of view. Fainter lines such as [OIV], [NeV] and H_2 (0-0)S1 will be observed in several tens of bright galaxies at 1<z<2, while diagnostic diagrams of active-nucleus vs star-formation activity will be feasible even for normal z~1 galaxies. We discuss the new parameter space that these future telescopes will cover and that strongly motivate their construction.Comment: Accepted for publication in The Astrophysical Journal on 20/10/2011, 17 pages, 13 figure