60 research outputs found
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
Non-essential role for TLR2 and its signaling adaptor Mal/TIRAP in preserving normal lung architecture in mice
Myeloid differentiation factor 88 (MyD88) and MyD88-adaptor like (Mal)/Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) play a critical role in transducing signals downstream of the Toll-like receptor (TLR) family. While genetic ablation of the TLR4/MyD88 signaling axis in mice leads to pulmonary cell death and oxidative stress culminating in emphysema, the involvement of Mal, as well as TLR2 which like TLR4 also signals via MyD88 and Mal, in the pathogenesis of emphysema has not been studied. By employing an in vivo genetic approach, we reveal here that unlike the spontaneous pulmonary emphysema which developed in Tlr42/2 mice by 6 months of age, the lungs of Tlr22/2 mice showed no physiological or morphological signs of emphysema. A more detailed comparative analysis of the lungs from these mice confirmed that elevated oxidative protein carbonylation levels and increased numbers of alveolar cell apoptosis were only detected in Tlr42/2 mice, along with up-regulation of NADPH oxidase 3 (Nox3) mRNA expression. With respect to Mal, the architecture of the lungs of Mal2/2 mice was normal. However, despite normal oxidative protein carbonylation levels in the lungs of emphysema-free Mal2/2 mice, these mice displayed increased levels of apoptosis comparable to those observed in emphysematous Tlr42/2 mice. In conclusion, our data provide in vivo evidence for the non-essential role for TLR2, unlike the related TLR4, in maintaining the normal architecture of the lung. In addition, we reveal that Mal differentially facilitates the anti-apoptotic, but not oxidant suppressive, activities of TLR4 in the lung, both of which appear to be essential for TLR4 to prevent the onset of emphysema
Radio & Optical Interferometry: Basic Observing Techniques and Data Analysis
Astronomers usually need the highest angular resolution possible, but the
blurring effect of diffraction imposes a fundamental limit on the image quality
from any single telescope. Interferometry allows light collected at
widely-separated telescopes to be combined in order to synthesize an aperture
much larger than an individual telescope thereby improving angular resolution
by orders of magnitude. Radio and millimeter wave astronomers depend on
interferometry to achieve image quality on par with conventional visible and
infrared telescopes. Interferometers at visible and infrared wavelengths extend
angular resolution below the milli-arcsecond level to open up unique research
areas in imaging stellar surfaces and circumstellar environments.
In this chapter the basic principles of interferometry are reviewed with an
emphasis on the common features for radio and optical observing. While many
techniques are common to interferometers of all wavelengths, crucial
differences are identified that will help new practitioners avoid unnecessary
confusion and common pitfalls. Concepts essential for writing observing
proposals and for planning observations are described, depending on the science
wavelength, angular resolution, and field of view required. Atmospheric and
ionospheric turbulence degrades the longest-baseline observations by
significantly reducing the stability of interference fringes. Such
instabilities represent a persistent challenge, and the basic techniques of
phase-referencing and phase closure have been developed to deal with them.
Synthesis imaging with large observing datasets has become a routine and
straightforward process at radio observatories, but remains challenging for
optical facilities. In this context the commonly-used image reconstruction
algorithms CLEAN and MEM are presented. Lastly, a concise overview of current
facilities is included as an appendix.Comment: 45 pages, 14 Figures; an abridged version of a chapter to appear in
Volume 2 of Planets, Stars and Stellar Systems, to be published in 2011 by
Springe
Preschool hyperactivity specifically elevates long-term mental health risks more strongly in males than females: a prospective longitudinal study through to young adulthood
Evidence of continuities between preschool hyperactivity and adult mental health problems highlight the potential value of targeting early identification and intervention strategies. However, specific risk factors are currently unclear. This large-scale prospective longitudinal study aimed to identify which hyperactive preschoolers are at greatest long-term risk of poor mental health. One hundred and seventy children (89 females) rated as hyperactive by their parents and 88 non-hyperactive controls (48 females) were identified from a community sample of 4,215 3 year-olds. Baseline data relating to behavioral/emotional problems and background characteristics were collected. Follow-up mental health and functional impairment outcomes were collected between 14 and 25 years of age. At age 3 years, males and females in the hyperactive group had similarly raised levels of hyperactivity and other behavior problems. In adolescence/young adulthood, these individuals showed elevated symptoms of ADHD, conduct disorder, mood disorder, anxiety and autism, as well as functional impairment. Preschool hyperactivity was strongly predictive of poor adolescent/adult outcomes for males across domains with effects being specifically driven by hyperactivity. For females, the effects of preschool hyperactivity were smaller and dropped to non-significant levels when other preschool problems were taken into account. Environmental risk factors also differed between the sexes, although these may also have been mediated by genetic risk. In conclusion, these results demonstrate marked sex differences in preschool predictors of later adolescent/adult mental health problems. Future research should include a measure of preschool inattention as well hyperactivity. The findings highlight the potential value of tailored approaches to early identification strategies
Attention training for infants at familial risk of ADHD (INTERSTAARS): study protocol for a randomised controlled trial
Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can
negatively impact on an individual’s quality of life. It is pathophysiologically complex and heterogeneous with
different neuropsychological processes being impaired in different individuals. Executive function deficits, including
those affecting attention, working memory and inhibitory control, are common. Cognitive training has been promoted
as a treatment option, based on the notion that by strengthening the neurocognitive networks underlying these
executive processes, ADHD symptoms will also be reduced. However, if implemented in childhood or later, when the
full disorder has become well-established, cognitive training has only limited value. INTERSTAARS is a trial designed to
test a novel approach to intervention, in which cognitive training is implemented early in development, before the
emergence of the disorder. The aim of INTERSTAARS is to train early executive skills, thereby increasing resilience and
reducing later ADHD symptoms and associated impairment.
Methods/design: Fifty 10–14-month-old infants at familial risk of ADHD will participate in INTERSTAARS. Infants
will be randomised to an intervention or a control group. The intervention aims to train early attention skills
by using novel eye-tracking technology and gaze-contingent training paradigms. Infants view animated games
on a screen and different events take place contingent on where on the screen the infant is looking. Infants
allocated to the intervention will receive nine weekly home-based attention training sessions. Control group
infants will also receive nine weekly home visits, but instead of viewing the training games during these visits
they will view non-gaze-contingent age-appropriate videos. At baseline and post treatment, infant attention
control will be assessed using a range of eye-tracking, observational, parent-report and neurophysiological
measures. The primary outcome will be a composite of eye-tracking tasks used to assess infant attention skills.
Follow-up data will be collected on emerging ADHD symptoms when the infants are 2 and 3 years old.
Discussion: This is the first randomised controlled trial to assess the potential efficacy of cognitive training as
a prevention measure for infants at familial risk of ADHD. If successful, INTERSTAARS could offer a promising
new approach for developing early interventions for ADHD.
Trial registration: International Standard Randomised Controlled Trial registry: ISRCTN37683928. Registered on
22 June 2015
Advances in understanding and treating ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability
Off-label psychopharmacologic prescribing for children: History supports close clinical monitoring
The review presents pediatric adverse drug events from a historical perspective and focuses on selected safety issues associated with off-label use of medications for the psychiatric treatment of youth. Clinical monitoring procedures for major psychotropic drug classes are reviewed. Prior studies suggest that systematic treatment monitoring is warranted so as to both minimize risk of unexpected adverse events and exposures to ineffective treatments. Clinical trials to establish the efficacy and safety of drugs currently being used off-label in the pediatric population are needed. In the meantime, clinicians should consider the existing evidence-base for these drugs and institute close clinical monitoring
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