Merger of Multiple Accreting Black Holes Concordant with Gravitational-wave Events

Recently, the advanced Laser Interferometer Gravitational-Wave Observatory (aLIGO) has detected black hole (BH) merger events, most of which are sourced by BHs more massive than 30 M-circle dot. Especially, the observation of GW170104 suggests dynamically assembled binaries favoring a distribution of misaligned spins. It has been argued that mergers of unassociated BHs can be engendered through a chance meeting in a multiple BH system under gas-rich environments. In this paper, we consider the merger of unassociated BHs, concordant with the massive BH merger events. To that end, we simulate a multiple BH system with a post-Newtonian N-body code incorporating gas accretion and general relativistic effects. As a result, we find that gas dynamical friction effectively promotes a three-body interaction of BHs in dense gas of n(gas) greater than or similar to 10(6) cm(-3), so that BH mergers can take place within 30 Myr. This scenario predicts an isotropic distribution of spin tilts. In the concordant models with GW150914, the masses of seed BHs are required to be greater than or similar to 25 M-circle dot. The potential sites of such chance meeting BH mergers are active galactic nucleus (AGN) disks and dense interstellar clouds. Assuming the LIGO O1, we roughly estimate the event rates for PopI BHs and PopIII BHs in AGN disks to be similar or equal to 1-2 yr(-1) and similar or equal to 1 yr(-1), respectively. Multiple episodes of AGNs may enhance the rates by roughly an order of magnitude. For massive PopI BHs in dense interstellar clouds the rate is similar or equal to 0.02 yr(-1). Hence, high-density AGN disks are a more plausible site for mergers of chance meeting BHs

Compact Object Mergers Driven by Gas Fallback

Recently, several gravitational wave detections have shown evidence for compact object mergers. However, the astrophysical origin of merging binaries is not well understood. Stellar binaries are typically at much larger separations than what is needed for the binaries to merge due to gravitational wave emission, which leads to the so-called final AU problem. In this Letter we propose a new channel for mergers of compact object binaries which solves the final AU problem. We examine the binary evolution following gas expansion due to a weak failed supernova explosion, neutrino mass loss, core disturbance, or envelope instability. In such situations the binary is possibly hardened by ambient gas. We investigate the evolution of the binary system after a shock has propagated by performing smoothed particle hydrodynamics simulations. We find that significant binary hardening occurs when the gas mass bound to the binary exceeds that of the compact objects. This mechanism represents a new possibility for the pathway to mergers for gravitational wave events

The Current Role of Androgen Deprivation in Patients Undergoing Dose-Escalated External Beam Radiation Therapy for Clinically Localized Prostate Cancer

Purpose. To review existing literature on the role of androgen deprivation therapy (ADT) with dose escalated radiation therapy. Methods and Materials. A PubMed search was undertaken to identify relevant articles. Results. Multiple recent studies were identified examining the role of ADT in the current era of radiation dose-escalation. Among the reviewed studies, varying radiation doses and techniques, ADT regimens, and patient selection criteria were utilized. Conflicting results were reported, with some studies demonstrating a benefit of delivering a higher radiation dose with ADT. Other studies failed to show significant benefits with the addition of ADT to dose-escalated RT. Conclusions. The benefit of adding ADT to dose-escalated RT is still uncertain. Prospective randomized trials, several of which are ongoing, are necessary to more adequately examine this issue. In the interim, physicians and patients should continue to utilize the existing data to weigh the risks and benefits of each approach to therapy

Prostate-Specific Membrane Antigen-Based Therapeutics

Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with 177Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials

Review of Salvage Therapy for Biochemically Recurrent Prostate Cancer: The Role of Imaging and Rationale for Systemic Salvage Targeted Anti-Prostate-Specific Membrane Antigen Radioimmunotherapy

Despite local therapy with curative intent, approximately 30% of men suffer from biochemical relapse. Though some of these PSA relapses are not life threatening, many men eventually progress to metastatic disease and die of prostate cancer. Local therapy is an option for some men, but many have progression of disease following local salvage attempts. One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed. Androgen deprivation therapy is a cornerstone of therapy in the salvage setting. While subsets may benefit in terms of delay in time to metastatic disease and/or death, research is ongoing to improve salvage systemic therapy. Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers. While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing. Salvage therapy and imaging modalities in this setting are briefly reviewed, and the rationale for PSMA-based systemic salvage radioimmunotherapy is described