SPH simulations of Shakura-Sunyaev instability at intermediate accretion rates

We show that a standard Shakura-Sunyaev accretion disc around a black hole with an accretion rate lower than the critical Eddington limit does show the instability in the radiation pressure dominated zone. We obtain this result performing time-dependent simulations of accretion disks for a set of values of the viscosity parameter and accretion rate. In particular we always find the occurrence of the collapse of the disc: the instability develops always towards a collapsed gas pressure dominated disc and not towards the expansion. This result is valid for all initial configurations we tested. We find significant convective heat flux that increases the instability development time, but is not strong enough to inhibit the disc collapse. A physical explanation of the lack of the expansion phase is proposed considering the role of the radial heat advection. Our finding is relevant since it excludes the formation of the hot comptonizing corona -often suggested to be present- around the central object by the mechanism of the Shakura-Sunyaev instability. We also show that, in the parameters range we simulated, accretion disks are crossed by significant amplitude acoustic waves.Comment: 8 pages, 12 Postscript figures, uses natbib.sty, accepted for publication in MNRA

Gaining the hard yard: pre-clinical evaluation of lentiviral-mediated gene therapy for the treatment of β-thalassemia

Gene therapy is one potential novel therapeutic avenue for the treatment of inherited monogenic disorders. Diseases of the blood are frequent targets for gene therapy because it is relatively easy to harvest haematopoietic stem cells (HSCs) from the bone marrow, genetically modify the cells ex vivo, and then re-administer the corrected cells back into the patient via intra-venous injection. In this Closeup, Milsom and Williams discuss the work of Roselli et al, who describe the pre-clinical evaluation of the treatment for β-thalassemia in erythroid cells via the genetic correction of patient HSCs using a lentiviral vector

Gravity in International Finance: Evidence From Fees on Equity Transactions

We shed light on the impact of institutional quality and information barriers on trade in financial services using a novel panel data set on revenue earned on domestic and crossborder equity securities underwriting transactions. Our data set covers 91,51

Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients

New insight into the causes, consequences, and correction of hematopoietic stem cell aging

Aging of hematopoietic stem cells (HSCs) is characterized by lineage bias, increased clonal expansion, and functional decrease. At the molecular level, aged HSCs typically display metabolic dysregulation, upregulation of inflammatory pathways, and downregulation of DNA repair pathways. Cellular aging of HSCs, driven by cell-intrinsic and cell-extrinsic factors, causes a predisposition to anemia, adaptive immune compromise, myelodys, plasia, and malignancy. Most hematologic diseases are strongly associated with age. But what is the biological foundation for decreased fitness with age? And are there therapeutic windows to resolve age-related hematopoietic decline? These questions were the focus of the International Society for Experimental Hematology (ISEH) New Investigator Committee Fall 2022 Webinar. This review touches on the latest insights from two leading laboratories into inflammatory- and niche-driven stem cell aging and includes speculation on strategies to prevent or correct age-related decline in HSC function

Two-Dimensional Hydrodynamic Simulations of Convection in Radiation-Dominated Accretion Disks

The standard equilibrium for radiation-dominated accretion disks has long been known to be viscously, thermally, and convectively unstable, but the nonlinear development of these instabilities---hence the actual state of such disks---has not yet been identified. By performing local two-dimensional hydrodynamic simulations of disks, we demonstrate that convective motions can release heat sufficiently rapidly as to substantially alter the vertical structure of the disk. If the dissipation rate within a vertical column is proportional to its mass, the disk settles into a new configuration thinner by a factor of two than the standard radiation-supported equilibrium. If, on the other hand, the vertically-integrated dissipation rate is proportional to the vertically-integrated total pressure, the disk is subject to the well-known thermal instability. Convection, however, biases the development of this instability toward collapse. The end result of such a collapse is a gas pressure-dominated equilibrium at the original column density.Comment: 10 pages, 7 figures, accepted for publication in ApJ. Please send comments to [email protected]

Effectiveness and reach of a directed-population approach to improving dental health and reducing inequalities: a cross sectional study

Background Childsmile School adopts a directed-population approach to target fluoride varnish applications to 20% of the primary one (P1) population in priority schools selected on the basis of the proportion of enrolled children considered to be at increased-risk of developing dental caries. The study sought to compare the effectiveness of four different methods for identifying individuals most in need when a directed-population approach is taken. <p></p> Methods The 2008 Basic National Dental Inspection Programme (BNDIP) cross-sectional P1 Scottish epidemiological survey dataset was used to model four methods and test three definitions of increased-risk. Effectiveness was determined by the positive predictive value (PPV) and explored in relation to 1-sensitivity and 1-specificity. <p></p> Results Complete data was available on 43470 children (87% of the survey). At the Scotland level, at least half (50%) of the children targeted were at increased-risk irrespective of the method used to target or the definition of increased-risk. There was no one method across all definitions of <i>increased-risk</i> that maximised PPV. Instead, PPV was highest when the targeting method complimented the definition of <i>increased-risk</i>. There was a higher percentage of children at <i>increased-risk</i> who were not targeted (1-sensitivity) when caries experience (rather than deprivation) was used to define <i>increased-risk</i>, irrespective of the method used for targeting. Over all three definitions of <i>increased-risk</i>, there was no one method that minimised (1-sensitivity) although this was lowest when the method and definition of <i>increased-risk</i> were complimentary. The false positive rate (1-specificity) for all methods and all definitions of <i>increased-risk</i> was consistently low (<20%), again being lowest when the method and definition of <i>increased-risk</i> were complimentary. <p></p> Conclusion Developing a method to reach all (or even the vast majority) of individuals at <i>increased-risk</i> defined by either caries experience or deprivation is difficult using a directed-population approach at a group level. There is a need for a wider debate between politicians and public health experts to decide how best to reach those most at need of intervention to improve health and reduce inequalities. <p></p&gt