Two-dimensional models of hydrodynamical accretion flows into black holes

We present a systematic numerical study of two-dimensional axisymmetric accretion flows around black holes. The flows have no radiative cooling and are treated in the framework of the hydrodynamical approximation. The models calculated in this study cover the large range of the relevant parameter space. There are four types of flows, determined by the values of the viscosity parameter $\alpha$ and the adiabatic index $\gamma$: convective flows, large-scale circulations, pure inflows and bipolar outflows. Thermal conduction introduces significant changes to the solutions, but does not create a new flow type. Convective accretion flows and flows with large-scale circulations have significant outward-directed energy fluxes, which have important implications for the spectra and luminosities of accreting black holes.Comment: 43 pages, 23 figures, submitted to Ap

Benefit of Apabetalone on Plasma Proteins in Renal Disease.

Introduction:Apabetalone, a small molecule inhibitor, targets epigenetic readers termed BET proteins that contribute to gene dysregulation in human disorders. Apabetalone has in vitro and in vivo anti-inflammatory and antiatherosclerotic properties. In phase 2 clinical trials, this drug reduced the incidence of major adverse cardiac events in patients with cardiovascular disease. Chronic kidney disease is associated with a progressive loss of renal function and a high risk of cardiovascular disease. We studied the impact of apabetalone on the plasma proteome in patients with impaired kidney function. Methods:Subjects with stage 4 or 5 chronic kidney disease and matched controls received a single dose of apabetalone. Plasma was collected for pharmacokinetic analysis and for proteomics profiling using the SOMAscan 1.3k platform. Proteomics data were analyzed with Ingenuity Pathway Analysis to identify dysregulated pathways in diseased patients, which were targeted by apabetalone. Results:At baseline, 169 plasma proteins (adjusted P value <0.05) were differentially enriched in renally impaired patients versus control subjects, including cystatin C and β2 microglobulin, which correlate with renal function. Bioinformatics analysis of the plasma proteome revealed a significant activation of 42 pathways that control immunity and inflammation, oxidative stress, endothelial dysfunction, vascular calcification, and coagulation. At 12 hours postdose, apabetalone countered the activation of pathways associated with renal disease and reduced the abundance of disease markers, including interleukin-6, plasminogen activator inhibitor-1, and osteopontin. Conclusion:These data demonstrated plasma proteome dysregulation in renally impaired patients and the beneficial impact of apabetalone on pathways linked to chronic kidney disease and its cardiovascular complications

Three-dimensional MHD Simulations of Radiatively Inefficient Accretion Flows

We present three-dimensional MHD simulations of rotating radiatively inefficient accretion flows onto black holes. In the simulations, we continuously inject magnetized matter into the computational domain near the outer boundary, and we run the calculations long enough for the resulting accretion flow to reach a quasi-steady state. We have studied two limiting cases for the geometry of the injected magnetic field: pure toroidal field and pure poloidal field. In the case of toroidal field injection, the accreting matter forms a nearly axisymmetric, geometrically-thick, turbulent accretion disk. The disk resembles in many respects the convection-dominated accretion flows found in previous numerical and analytical investigations of viscous hydrodynamic flows. Models with poloidal field injection evolve through two distinct phases. In an initial transient phase, the flow forms a relatively flattened, quasi-Keplerian disk with a hot corona and a bipolar outflow. However, when the flow later achieves steady state, it changes in character completely. The magnetized accreting gas becomes two-phase, with most of the volume being dominated by a strong dipolar magnetic field from which a thermal low-density wind flows out. Accretion occurs mainly via narrow slowly-rotating radial streams which `diffuse' through the magnetic field with the help of magnetic reconnection events.Comment: 35 pages including 3 built-in plots and 14 separate jpg-plots; version accepted by Ap

On the Radial Structure of Radiatively Inefficient Accretion Flows with Convection

We consider the radial structure of radiatively inefficient hydrodynamic accretion flows around black holes. We show that low-viscosity flows consist of two zones: an outer convection-dominated zone and an inner advection-dominated zone. The transition between these two zones occurs at ~50 Schwarzschild radii.Comment: 11 pages, 3 figures, accepted for publication in Ap

Hydrodynamical Non-radiative Accretion Flows in Two-Dimensions

Two-dimensional (axially symmetric) numerical hydrodynamical calculations of accretion flows which cannot cool through emission of radiation are presented. The calculations begin from an equilibrium configuration consisting of a thick torus with constant specific angular momentum. Accretion is induced by the addition of a small anomalous azimuthal shear stress which is characterized by a function \nu. We study the flows generated as the amplitude and form of \nu are varied. A spherical polar grid which spans more than two orders of magnitude in radius is used to resolve the flow over a wide range of spatial scales. We find that convection in the inner regions produces significant outward mass motions that carry away both the energy liberated by, and a large fraction of the mass participating in, the accretion flow. Although the instantaneous structure of the flow is complex and dominated by convective eddies, long time averages of the dynamical variables show remarkable correspondence to certain steady-state solutions. Near the equatorial plane, the radial profiles of the time-averaged variables are power-laws with an index that depends on the radial scaling of the shear stress. We find that regardless of the adiabatic index of the gas, or the form or magnitude of the shear stress, the mass inflow rate is a strongly increasing function of radius, and is everywhere nearly exactly balanced by mass outflow. The net mass accretion rate through the disc is only a fraction of the rate at which mass is supplied to the inflow at large radii, and is given by the local, viscous accretion rate associated with the flow properties near the central object.Comment: 33 pages, 12 figures, accepted by MNRA

ARTISTIC: A randomised trial of human papillomavirus (HPV) testing in primary cervical screening

The official published version of the article can be found at the link below.Objectives: Primary cervical screening uses cytology to detect cancer precursor lesions [cervical intraepithelial neoplasia stage 3 or beyond (CIN3+)]. Human papillomavirus (HPV) testing could add sensitivity as an adjunct to cytology or as a first test, reserving cytology for HPV-positive women. This study addresses the questions: Does the combination of cytology and HPV testing achieve a reduction in incident CIN3+?; Is HPV testing cost-effective in primary cervical screening?; Is its use associated with adverse psychosocial or psychosexual effects?; and How would it perform as an initial screening test followed by cytology for HPV positivity? Design: ARTISTIC was a randomised trial of cervical cytology versus cervical cytology plus HPV testing, evaluated over two screening rounds, 3 years apart. Round 1 would detect prevalent disease and round 2 a combination of incident and undetected disease from round 1. Setting: Women undergoing routine cervical screening in the NHS programme in Greater Manchester. Participants: In total 24,510 women aged 20–64 years were enrolled between July 2001 and September 2003. Interventions: HPV testing was performed on the liquid-based cytology (LBC) sample obtained at screening. Women were randomised in a ratio of 3:1 to have the HPV test result revealed and acted upon if persistently positive in cytology-negative cases or concealed. A detailed health economic evaluation and a psychosocial and psychosexual assessment were also performed. Main outcome measures: The primary outcome was CIN3+ in round 2. Secondary outcomes included an economic assessment and psychosocial effects. A large HPV genotyping study was also conducted. Results: In round 1 there were 313 CIN3+ lesions, representing a prevalence in the revealed and concealed arms of 1.27% and 1.31% respectively (p = 0.81). Round 2 (30–48 months) involved 14,230 (58.1%) of the women screened in round 1 and only 31 CIN3+ were detected; the CIN3 rate was not significantly different between the revealed and concealed arms. A less restrictive definition of round 2 (26–54 months) increased CIN3+ to 45 and CIN3+ incidence in the arms was significantly different (p = 0.05). There was no difference in CIN3+ between the arms when rounds 1 and 2 were combined. Prevalence of highrisk HPV types was age-dependent. Overall prevalence of HPV16/18 increased with severity of yskaryosis. Mean costs per woman in round 1 were £72 and £56 for the revealed and concealed arms (p < 0.001); an age-adjustment reduced these mean costs to £65 and £52. Incremental cost-effectiveness ratio for detecting additional CIN3+ by adding HPV testing to LBC screening in round 1 was £38,771. Age-adjusted mean cost for LBC primary screening with HPV triage was £39 compared with £48 for HPV primary screening with LBC triage. HPV testing did not appear to cause significant psychosocial distress. Conclusions: Routine HPV testing did not add significantly to the effectiveness of LBC in this study. No significant adverse psychosocial effects were detected. It would not be cost-effective to screen with cytology and HPV combined but HPV testing, as either triage or initial test triaged by cytology, would be cheaper than cytology without HPV testing. LBC would not benefit from combination with HPV; it is highly effective as primary screening but HPV testing has twin advantages of high negative predictive value and automated platforms enabling high throughput. HPV primary screening would require major contraction and reconfiguration of laboratory services. Follow-up continues in ARTISTIC while maintaining concealment for a further 3-year round of screening, which will help in screening protocol development for the post-vaccination era

Assessing methods for representing soil heterogeneity through a flexible approach within the Joint UK Land Environment Simulator (JULES) at version 3.4.1

The interactions between the land surface and the atmosphere can impact weather and climate through the exchanges of water, energy, carbon and momentum. The properties of the land surface are important when modelling these exchanges correctly especially with models being used at increasingly higher resolution. The Joint UK Land Environment Simulator (JULES) currently uses a tiled representation of land cover but can only model a single dominant soil type within a grid box. Hence, there is no representation of sub-grid-scale soil heterogeneity. This paper introduces and evaluates a new flexible surface–soil tiling scheme in JULES. Several different soil tiling approaches are presented for a synthetic case study. The changes to model performance have been compared to the current single-soil scheme and a high-resolution “Truth” scenario. Results have shown that the different soil tiling strategies do have an impact on the water and energy exchanges due to the way vegetation accesses the soil moisture. Tiling the soil according to the surface type, with the soil properties set to the dominant soil type under each surface is the best performing configuration. The results from this setup simulate water and energy fluxes that are the closest to the high-resolution Truth scenario but require much less information on the soil type than the high-resolution soil configuration.</p

RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease

AbstractHigh density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of cardiovascular disease (CVD) by removing excess cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk