Theory of disk accretion onto supermassive black holes

Accretion onto supermassive black holes produces both the dramatic phenomena associated with active galactic nuclei and the underwhelming displays seen in the Galactic Center and most other nearby galaxies. I review selected aspects of the current theoretical understanding of black hole accretion, emphasizing the role of magnetohydrodynamic turbulence and gravitational instabilities in driving the actual accretion and the importance of the efficacy of cooling in determining the structure and observational appearance of the accretion flow. Ongoing investigations into the dynamics of the plunging region, the origin of variability in the accretion process, and the evolution of warped, twisted, or eccentric disks are summarized.Comment: Mostly introductory review, to appear in "Supermassive black holes in the distant Universe", ed. A.J. Barger, Kluwer Academic Publishers, in pres

Statin use is associated with fewer periodontal lesions: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Inflammatory processes are considered to participate in the development of cardiovascular disease (CVD). Statins have been used successfully in the prevention and treatment of coronary heart disease. Chronic periodontitis has been suggested to contribute to CVD. The aim of this study was to examine the association of statin use and clinical markers of chronic periodontitis.</p> <p>Methods</p> <p>Periodontal probing pocket depth (PPD) values were collected from dental records of 100 consecutive adult patients referred to a university dental clinic for treatment of advanced chronic periodontitis. A novel index, Periodontal Inflammatory Burden Index (PIBI), was derived from the PPD values to estimate systemic effects of periodontitis.</p> <p>Results</p> <p>Periodontitis patients taking statins had a 37% lower number of pathological periodontal pockets than those without statin medication (P = 0.00043). PIBI, which combines and unifies the data on PPD, was 40% smaller in statin using patients than in patients without statin (P = 0.00069). PIBI of subjects on simvastatin and atorvastatin both differed significantly from patients without statin and were on the same level. The subjects' number of teeth had no effect on the results</p> <p>Conclusion</p> <p>Patients on statin medication exhibit fewer signs of periodontal inflammatory injury than subjects without the statin regimen. PIBI provides a tool for monitoring inflammatory load of chronic periodontitis. The apparent beneficial effects of statins may in part be mediated by their pleiotropic anti-inflammatory effect on periodontal tissue.</p

APOBEC3G-Induced Hypermutation of Human Immunodeficiency Virus Type-1 Is Typically a Discrete “All or Nothing” Phenomenon

The rapid evolution of Human Immunodeficiency Virus (HIV-1) allows studies of ongoing host–pathogen interactions. One key selective host factor is APOBEC3G (hA3G) that can cause extensive and inactivating Guanosine-to-Adenosine (G-to-A) mutation on HIV plus-strand DNA (termed hypermutation). HIV can inhibit this innate anti-viral defense through binding of the viral protein Vif to hA3G, but binding efficiency varies and hypermutation frequencies fluctuate in patients. A pivotal question is whether hA3G-induced G-to-A mutation is always lethal to the virus or if it may occur at sub-lethal frequencies that could increase viral diversification. We show in vitro that limiting-levels of hA3G-activity (i.e. when only a single hA3G-unit is likely to act on HIV) produce hypermutation frequencies similar to those in patients and demonstrate in silico that potentially non-lethal G-to-A mutation rates are ∼10-fold lower than the lowest observed hypermutation levels in vitro and in vivo. Our results suggest that even a single incorporated hA3G-unit is likely to cause extensive and inactivating levels of HIV hypermutation and that hypermutation therefore is typically a discrete “all or nothing” phenomenon. Thus, therapeutic measures that inhibit the interaction between Vif and hA3G will likely not increase virus diversification but expand the fraction of hypermutated proviruses within the infected host

Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation

BACKGROUND: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. METHODS/PRINCIPAL FINDINGS: Pregnant sheep received adequate (1.0M; CE, n = 6) or energy restricted (0.7M) diet during early (1-65 days; LEE, n = 6) or late (65-128 days; LEL, n = 7) gestation (term approximately 147 days). Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT) and body composition determination by dual energy x-ray absorptiometry (DXA). All animals were then exposed to an obesogenic environment for 6-7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were 'lean' (1.5 years). Obesity revealed generalised metabolic 'inflexibility' and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulin(AUC) (from 133 to 341 [s.e.d. 26] ng.ml(-1).120 mins) during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] ng.ml(-1)) and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16] ng.ml(-1); LEL male vs. CE male, respectively). Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. CONCLUSIONS: This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and 'reveals' programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young prenatally 'programmed' animals so long as weight is adequately controlled. Nutritional excess in adulthood exacerbates any programmed phenotype, indicating greater vigilance over weight control is required for those individuals exposed to nutritional thrift during gestation

From recommendation to action: psychosocial factors influencing physician intention to use Health Technology Assessment (HTA) recommendations

BACKGROUND: Evaluating the impact of recommendations based upon health technology assessment (HTA) represents a challenge for both HTA agencies and healthcare policy-makers. Using a psychosocial theoretical framework, this study aimed at exploring the factors affecting physician intention to adopt HTA recommendations. The selected recommendations were prioritisation systems for patients on waiting lists for two surgical procedures: hip and knee replacement and cataract surgery. METHODS: Determinants of physician intention to use HTA recommendations for patient prioritisation were assessed by a questionnaire based upon the Theory of Interpersonal Behaviour. A total of 96 physicians from two medical specialties (ophthalmology and orthopaedic surgery) responded to the questionnaire (response rate 44.2%). A multiple analysis of variance (MANOVA) was performed to assess differences between medical specialties on the set of theoretical variables. Given the main effect difference between specialties, two regression models were tested separately to assess the psychosocial determinants of physician intention to use HTA recommendations for the prioritisation of patients on waiting lists for surgical procedures. RESULTS: Factors influencing physician intention to use HTA recommendations differ between groups of specialists. Intention to use the prioritisation system for patients on waiting lists for cataract surgery among ophthalmologists was related to attitude towards the behaviour, social norms, as well as personal normative beliefs. Intention to use HTA recommendations for patient prioritisation for hip and knee replacement among orthopaedic surgeons was explained by: perception of conditions that facilitated the realisation of the behaviour, personal normative beliefs, and habit of using HTA recommendations in clinical work. CONCLUSION: This study offers a model to assess factors influencing the intention to adopt recommendations from health technology assessment into professional practice. Results identify determinant factors that should be considered in the elaboration of strategies to support the implementation of evidence-based practice, with respect to emerging health technologies and modalities of practice. However, it is important to emphasise that behavioural determinants of evidence-based practice vary according to the specific technology considered. Evidence-based implementation of HTA recommendations, as well as other evidence-based practices, should build on a theoretical understanding of the complex forces that shape the practice of healthcare professionals

Complications and pitfalls of lumbar interlaminar and transforaminal epidural injections

Lumbar interlaminar and transforaminal epidural injections are used in the treatment of lumbar radicular pain and other lumbar spinal pain syndromes. Complications from these procedures arise from needle placement and the administration of medication. Potential risks include infection, hematoma, intravascular injection of medication, direct nerve trauma, subdural injection of medication, air embolism, disc entry, urinary retention, radiation exposure, and hypersensitivity reactions. The objective of this article is to review the complications of lumbar interlaminar and transforaminal epidural injections and discuss the potential pitfalls related to these procedures. We performed a comprehensive literature review through a Medline search for relevant case reports, clinical trials, and review articles. Complications from lumbar epidural injections are extremely rare. Most if not all complications can be avoided by careful technique with accurate needle placement, sterile precautions, and a thorough understanding of the relevant anatomy and contrast patterns on fluoroscopic imaging

A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association at Chromosome 9q33.2

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease affecting both joints and extra-articular tissues. Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability. To identify additional susceptibility loci, we carried out a multi-tiered, case-control association study, genotyping 25,966 putative functional SNPs in 475 white North American RA patients and 475 matched controls. Significant markers were genotyped in two additional, independent, white case-control sample sets (661 cases/1322 controls from North America and 596 cases/705 controls from The Netherlands) identifying a SNP, rs1953126, on chromosome 9q33.2 that was significantly associated with RA (ORcommon = 1.28, trend Pcomb = 1.45E-06). Through a comprehensive fine-scale-mapping SNP-selection procedure, 137 additional SNPs in a 668 kb region from MEGF9 to STOM on 9q33.2 were chosen for follow-up genotyping in a staged-approach. Significant single marker results (Pcomb<0.01) spanned a large 525 kb region from FBXW2 to GSN. However, a variety of analyses identified SNPs in a 70 kb region extending from the third intron of PHF19 across TRAF1 into the TRAF1-C5 intergenic region, but excluding the C5 coding region, as the most interesting (trend Pcomb: 1.45E-06 → 5.41E-09). The observed association patterns for these SNPs had heightened statistical significance and a higher degree of consistency across sample sets. In addition, the allele frequencies for these SNPs displayed reduced variability between control groups when compared to other SNPs. Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential

Planck intermediate results. XXI. Comparison of polarized thermal emission from Galactic dust at 353 GHz with interstellar polarization in the visible

The Planck survey provides unprecedented full-sky coverage of the submillimetre polarized emission from Galactic dust. In addition to the information on the direction of the Galactic magnetic field, this also brings new constraints on the properties of dust. The dust grains that emit the radiation seen by Planck in the submillimetre also extinguish and polarize starlight in the visible. Comparison of the polarization of the emission and of the interstellar polarization on selected lines of sight probed by stars provides unique new diagnostics of the emission and light scattering properties of dust, and therefore of the important dust model parameters, composition, size, and shape. Using ancillary catalogues of interstellar polarization and extinction of starlight, we obtain the degree of polarization, p(V), and the optical depth in the V band to the star, tau(V). Toward these stars we measure the submillimetre polarized intensity, P-S, and total intensity, I-S,I- in the Planck 353 GHz channel. We compare the column density measure in the visible, E(B - V), with that inferred from the Planck product map of the submillimetre dust optical depth and compare the polarization direction (position angle) in the visible with that in the submillimetre. For those lines of sight through the di ff use interstellar medium with comparable values of the estimated column density and polarization directions close to orthogonal, we correlate properties in the submillimetre and visible to find two ratios, R-S/V = (P-S/I-S) = (p(V)/tau(V)) and R-P/p = P-S/p(V), the latter focusing directly on the polarization properties of the aligned grain population alone. We find R-S/V = 4.2, with statistical and systematic uncertainties 0.2 and 0.3, respectively, and R-P/p = 5.4 MJy sr(-1), with uncertainties 0.2 and 0.3 MJy sr(-1), respectively. Our estimate of R-S/V is compatible with predictions based on a range of polarizing dust models that have been developed for the di ff use interstellar medium. This estimate provides new empirical validation of many of the common underlying assumptions of the models, but is not yet very discriminating among them. However, our estimate of R-P/p is not compatible with predictions, which are too low by a factor of about 2.5. This more discriminating diagnostic, R-P/p, indicates that changes to the optical properties in the models of the aligned grain population are required. These new diagnostics, together with the spectral dependence in the submillimetre from Planck, will be important for constraining and understanding the full complexity of the grain models, and for interpreting the Planck thermal dust polarization and refinement of the separation of this contamination of the cosmic microwave background.Peer reviewe