Direct Collapse to Supermassive Black Hole Seeds: Comparing the AMR and SPH Approaches

We provide detailed comparison between the AMR code Enzo-2.4 and the SPH/N- body code GADGET-3 in the context of isolated or cosmological direct baryonic collapse within dark matter (DM) halos to form supermassive black holes. Gas flow is examined by following evolution of basic parameters of accretion flows. Both codes show an overall agreement in the general features of the collapse, however, many subtle differences exist. For isolated models, the codes increase their spatial and mass resolutions at different pace, which leads to substantially earlier collapse in SPH than in AMR cases due to higher gravitational resolution in GADGET-3. In cosmological runs, the AMR develops a slightly higher baryonic resolution than SPH during halo growth via cold accretion permeated by mergers. Still, both codes agree in the buildup of DM and baryonic structures. However, with the onset of collapse, this difference in mass and spatial resolution is amplified, so evolution of SPH models begins to lag behind. Such a delay can have effect on formation/destruction rate of H2 due to UV background, and on basic properties of host halos. Finally, isolated non-cosmological models in spinning halos, with spin parameter {\lambda} ~ 0.01 - 0.07, show delayed collapse for greater {\lambda}, but pace of this increase is faster for AMR. Within our simulation setup, GADGET-3 requires significantly larger computational resources than Enzo- 2.4 during collapse, and needs similar resources, during the pre-collapse, cosmological structure formation phase. Yet it benefits from substantially higher gravitational force and hydrodynamic resolutions, except at the end of collapse.Comment: 19 pages, 14 figures, Referees' comments incorporated. Accepted for publication in MNRA

Cochlea-sparing acoustic neuroma treatment with 4π radiation therapy.

PurposeThis study investigates whether 4π noncoplanar radiation therapy can spare the cochleae and consequently potentially improve hearing preservation in patients with acoustic neuroma who are treated with radiation therapy.Methods and materialsClinical radiation therapy plans for 30 patients with acoustic neuroma were included (14 stereotactic radiation surgery [SRS], 6 stereotactic radiation therapy [SRT], and 10 intensity modulated radiation therapy [IMRT]). The 4π plans were created for each patient with 20 optimal beams selected using a greedy column generation method and subsequently recalculated in Eclipse for comparison. Organ-at-risk (OAR) doses, homogeneity index, conformity, and tumor control probability (TCP) were compared. Normal tissue complication probability (NTCP) was calculated for sensorineural hearing loss (SNHL) at 3 and 5 years posttreatment. The dose for each plan was then escalated to achieve 99.5% TCP.Results4π significantly reduced the mean dose to both cochleae by 2.0 Gy (32%) for SRS, 3.2 Gy (29%) for SRT, and 10.0 Gy (32%) for IMRT. The maximum dose to both cochleae was also reduced with 4π by 1.6 Gy (20%), 2.2 Gy (15%), and 7.1 Gy (18%) for SRS, SRT, and IMRT plans, respectively. The reductions in mean/maximum brainstem dose with 4π were also statistically significant. Mean doses to other OARs were reduced by 19% to 56% on average. 4π plans had a similar CN and TCP, with a significantly higher average homogeneity index (0.93 vs 0.92) and significantly lower average NTCP for SNHL at both 3 years (30.8% vs 40.8%) and 5 years (43.3% vs 61.7%). An average dose escalation of approximately 116% of the prescription dose achieved 99.5% TCP, which resulted in 32.6% and 43.4% NTCP for SNHL at 3 years and 46.4% and 64.7% at 5 years for 4π and clinical plans, respectively.ConclusionsCompared with clinical planning methods, optimized 4π radiation therapy enables statistically significant sparing of the cochleae in acoustic neuroma treatment as well as lowering of other OAR doses, potentially reducing the risk of hearing loss

Direct Collapse to Supermassive Black Hole Seeds with Radiative Transfer: Isolated Halos

Direct collapse within dark matter (DM) halos is a promising path to form supermassive black hole (SMBH) seeds at high redshifts. The outer part of this collapse remains optically thin, and has been studied intensively using numerical simulations. However, the innermost region of the collapse is expected to become optically thick and requires us to follow the radiation field in order to understand its subsequent evolution. So far, the adiabatic approximation has been used exclusively for this purpose. We apply radiative transfer in the flux-limited diffusion (FLD) approximation to solve the evolution of coupled gas and radiation, for isolated halos. For direct collapse within isolated DM halos, we find that (1) the photosphere forms at ~10^{-6} pc and rapidly expands outward. (2) A central core forms, with a mass of ~1 Mo, supported by thermal gas pressure gradients and rotation. (3) Growing thermal gas and radiation pressure gradients dissolve it. (4) This process is associated with a strong anisotropic outflow, and another core forms nearby and grows rapidly. (5) Typical radiation luminosity emerging from the photosphere encompassing these cores is ~5 x 10^{37}-5 x 10^{38} erg/s, of order the Eddington luminosity. (6) Two variability timescales are associated with this process: a long one, which is related to the accretion flow within the central ~10^{-4}-10^{-3} pc, and ~0.1 yr, which is related to radiation diffusion. (7) Adiabatic models have been run for comparison and their evolution differs profoundly from that of the FLD models, by forming a central geometrically-thick disk. Overall, an adiabatic equation of state is not a good approximation to the advanced stage of direct collapse, mainly because the radiation in the FLD is capable of escaping due to anisotropy in the optical depth and associated gradients.Comment: 19 pages, 17 figures, MNRAS, in press; correcting typo

Superior Semicircular Canal Dehiscence in a Patient with Ehlers-Danlos Syndrome: A Case Report.

Superior semicircular canal dehiscence (SSCD) is a bony defect in the middle cranial fossa floor that results in an abnormal connection between the inner ear and cranial vault. Although the etiology of SSCD remains unclear, an inappropriately thin or fragile temporal bone likely predisposes an individual towards developing SSCD. Ehlers-Danlos syndrome (EDS) constitutes a group of genetic connective tissue disorders caused by a defect in the production, processing, or structure of collagen, or its associated proteins. The possible association between SSCD and EDS has not been previously described in the literature. We herein report a case of a 50-year-old female with EDS-hypermobility type who presented with a 15-year history of migraines, vertigo, and tinnitus. The patient was subsequently diagnosed with bilateral SSCD and underwent a right middle fossa (pre-auricular infratemporal) craniotomy for SSCD repair. She reported significant improvement in her auditory and vestibular symptoms, with the exception of continued mild dizziness and disequilibrium at the 3-month follow-up. Due to the rare reports of auditory symptoms in EDS, this case study highlights the importance of considering an otological consultation for auditory manifestations in a patient with EDS and illustrates a potential association between EDS and SSCD

Current trends in glioblastoma multiforme treatment: radiation therapy and immune checkpoint inhibitors.

Glioblastoma multiforme (GBM) is the most common primary brain cancer. Even with aggressive combination therapy, the median life expectancy for patients with GBM remains approximately 14 months. In order to improve the outcomes of patients with GBM, the development of newer treatments is critical. The concept of using the immune system as a therapeutic option has been suggested for several decades; by harnessing the body's adaptive immune mechanisms, immunotherapy could provide a durable and targeted treatment against cancer. However, many cancers, including GBM, have developed mechanisms that protect tumor cells from being recognized and eliminated by the immune system. For new immunotherapeutic regimens to be successful, overcoming immunosuppression via immune checkpoint signaling should be taken into consideration

Impact of Human Immunodeficiency Virus in the Pathogenesis and Outcome of Patients with Glioblastoma Multiforme.

BackgroundImprovement in antiviral therapies have been accompanied by an increased frequency of non-Acquired Immune Deficiency Syndrome (AIDS) defining malignancies, such as glioblastoma multiforme. Here, we investigated all reported cases of human immunodeficiency virus (HIV)-positive patients with glioblastoma and evaluated their clinical outcomes. A comprehensive review of the molecular pathogenetic mechanisms underlying glioblastoma development in the setting of HIV/AIDS is provided.MethodsWe performed a PubMed search using keywords "HIV glioma" AND "glioblastoma," and "AIDS glioma" AND "glioblastoma." Case reports and series describing HIV-positive patients with glioblastoma (histologically-proven World Health Organization grade IV astrocytoma) and reporting on HAART treatment status, clinical follow-up, and overall survival (OS), were included for the purposes of quantitative synthesis. Patients without clinical follow-up data or OS were excluded. Remaining articles were assessed for data extraction eligibility.ResultsA total of 17 patients met our inclusion criteria. Of these patients, 14 (82.4%) were male and 3 (17.6%) were female, with a mean age of 39.5±9.2 years (range 19-60 years). Average CD4 count at diagnosis of glioblastoma was 358.9±193.4 cells/mm3. Tumor progression rather than AIDS-associated complications dictated patient survival. There was a trend towards increased median survival with HAART treatment (12.0 vs 7.5 months, p=0.10).ConclusionOur data suggests that HAART is associated with improved survival in patients with HIV-associated glioblastoma, although the precise mechanisms underlying this improvement remain unclear

Direct Collapse to Supermassive Black Hole Seeds with Radiation Transfer: Cosmological Halos

We have modeled direct collapse of a primordial gas within dark matter halos in the presence of radiative transfer, in high-resolution zoom-in simulations in a cosmological framework, down to the formation of the photosphere and the central object. Radiative transfer has been implemented in the flux-limited diffusion (FLD) approximation. Adiabatic models were run for comparison. We find that (a) the FLD flow forms an irregular central structure and does not exhibit fragmentation, contrary to adiabatic flow which forms a thick disk, driving a pair of spiral shocks, subject to Kelvin-Helmholtz shear instability forming fragments; (b) the growing central core in the FLD flow quickly reaches ~10 Mo and a highly variable luminosity of 10^{38}-10^{39} erg/s, comparable to the Eddington luminosity. It experiences massive recurrent outflows driven by radiation force and thermal pressure gradients, which mix with the accretion flow and transfer the angular momentum outwards; and (c) the interplay between these processes and a massive accretion, results in photosphere at ~10 AU. We conclude that in the FLD model (1) the central object exhibits dynamically insignificant rotation and slower than adiabatic temperature rise with density; (2) does not experience fragmentation leading to star formation, thus promoting the fast track formation of a supermassive black hole (SMBH) seed; (3) inclusion of radiation force leads to outflows, resulting in the mass accumulation within the central 10^{-3} pc, which is ~100 times larger than characteristic scale of star formation. The inclusion of radiative transfer reveals complex early stages of formation and growth of the central structure in the direct collapse scenario of SMBH seed formation.Comment: 19 pages, 16 figures, MNRAS, accepted for publicatio

American Association for Cancer Research Genetics and Biology of Brain Cancers 2009, December 13–15, 2009, San Diego, CA

Molecularly targeted therapies promise to transform the treatment of cancer patients, including those with brain tumors. A deeper understanding of the biology of brain tumors has led to a palpable excitement that new and more effective treatments are on the horizon for these deadly diseases. This conference brought basic, genomic, and translational scientists together with clinicians to discuss how to develop more effective molecularly targeted therapies for brain tumor patients based on a mechanistic understanding of the molecular circuitry and biology of the disease

Direct Collapse to Precursors of Supermassive Black Hole Seeds:Radiation Feedback-Generated Outflows

We use high-resolution zoom-in cosmological simulations to model outflow triggered by radiation and thermal drivers around the central mass accumulation during direct collapse within the dark matter (DM) halo. The maximal resolution is $1.3\times 10^{-5}$ pc, and no restrictions are put on the geometry of the inflow/outflow. The central mass is considered {\it prior} to the formation of the supermassive black hole seed at redshift of $z\sim 15.9$, and can constitute either a supermassive star (SMS) of $\sim 10^5\,M_\odot$ surrounded by growing accretion disk or a self-gravitating disk. The radiation transfer is modeled using the ray-tracing algorithm. Due to the high accretion rate of $\sim 1\,M_\odot\,{\rm yr^{-1}}$ determined by the DM halo, accretion is supercritical, resulting in supercritical luminosity which affects the inflow rate, with the duty cycle of $\sim 0.9$. We observe a fast development of hot cavities which quickly extend into polar funnels and expanding dense shells. Within the funnels, fast winds, $\sim 10^3\,{\rm km\,s^{-1}}$, are mass-loaded by the accreting gas. We follow the expanding shells to $\sim 1$ pc, when the shell velocity remains substantially, $\sim 5$ times, above the escape speed. The ionization cones formed by the central UV/X-ray flux extend to the halo virial radius, $R_{\rm h}$. Extrapolating the outflow properties shows that the halo material outside the shell will have difficulty to stop it. We therefore conclude that the expanding wind-driven shell will breakout of the central parsec and will reach $\sim R_{\rm h}$. Finally, the anisotropic accretion flow on sub-parsec scales will attenuate the soft X-rays effect on the H$_2$. Hence, formation of funnels and powerful outflows around, e.g., SMS, can have interesting observational corollaries, to be addressed elsewhere.Comment: 20 pages, 13 figures, submitted to Ap