The relationship between sleep and behavior in autism spectrum disorder (ASD): a review

Although there is evidence that significant sleep problems are common in children with autism spectrum disorder (ASD) and that poor sleep exacerbates problematic daytime behavior, such relationships have received very little attention in both research and clinical practice. Treatment guidelines to help manage challenging behaviors in ASD fail to mention sleep at all, or they present a very limited account. Moreover, limited attention is given to children with low-functioning autism, those individuals who often experience the most severe sleep disruption and behavioral problems. This paper describes the nature of sleep difficulties in ASD and highlights the complexities of sleep disruption in individuals with low-functioning autism. It is proposed that profiling ASD children based on the nature of their sleep disruption might help to understand symptom and behavioral profiles (or vice versa) and therefore lead to better-targeted interventions. This paper concludes with a discussion of the limitations of current knowledge and proposes areas that are important for future research. Treating disordered sleep in ASD has great potential to improve daytime behavior and family functioning in this vulnerable population

Differences in the perceived impact of sleep deprivation among surgical and non-surgical residents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72096/1/j.1365-2923.2007.02963.x.pd

Efficacy and Safety of Dabrafenib in Pediatric Patients with BRAF V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study

PURPOSE: Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor. Patients with BRAF V600 mutation-positive pLGG may benefit from treatment with dabrafenib. Part 2 of a phase I/IIa study, open-label study (NCT01677741) explores the activity and safety of dabrafenib treatment in these patients. PATIENTS AND METHODS: Patients ages 1 to <18 years who had BRAF V600-mutant solid tumors (≥1 evaluable lesion) with recurrent, refractory, or progressive disease after ≥1 standard therapy were treated with oral dabrafenib 3.0 to 5.25 mg/kg/day (part 1) or at the recommended phase II dose (RP2D; part 2). Primary objectives were to determine the RP2D (part 1, results presented in a companion paper) and assess clinical activity (part 2). Here, we report the clinical activity, including objective response rates (ORRs) using Response Assessment in Neuro-Oncology criteria and safety across parts 1 and 2. RESULTS: Overall, 32 patients with pLGG were enrolled (part 1, n = 15; part 2, n = 17). Minimum follow-up was 26.2 months. Among all patients, the ORR was 44% [95% confidence interval (CI), 26-62] by independent review. The 1-year progression-free survival rate was 85% (95% CI, 64-94). Treatment-related adverse events (AE) were reported in 29 patients (91%); the most common was fatigue (34%). Grade 3/4 treatment-related AEs were reported in 9 patients (28%). CONCLUSIONS: Dabrafenib demonstrated meaningful clinical activity and acceptable tolerability in patients with BRAF V600-mutant pLGG

Models of Star-Planet Magnetic Interaction

Magnetic interactions between a planet and its environment are known to lead to phenomena such as aurorae and shocks in the solar system. The large number of close-in exoplanets that were discovered triggered a renewed interest in magnetic interactions in star-planet systems. Multiple other magnetic effects were then unveiled, such as planet inflation or heating, planet migration, planetary material escape, and even modification of the host star properties. We review here the recent efforts in modelling and understanding magnetic interactions between stars and planets in the context of compact systems. We first provide simple estimates of the effects of magnetic interactions and then detail analytical and numerical models for different representative scenarii. We finally lay out a series of future developments that are needed today to better understand and constrain these fascinating interactions.Comment: 23 pages, 10 figures, accepted as a chapter in the Handbook of Exoplanet

Signatures of Star-planet interactions

Planets interact with their host stars through gravity, radiation and magnetic fields, and for those giant planets that orbit their stars within $\sim$10 stellar radii ($\sim$0.1 AU for a sun-like star), star-planet interactions (SPI) are observable with a wide variety of photometric, spectroscopic and spectropolarimetric studies. At such close distances, the planet orbits within the sub-alfv\'enic radius of the star in which the transfer of energy and angular momentum between the two bodies is particularly efficient. The magnetic interactions appear as enhanced stellar activity modulated by the planet as it orbits the star rather than only by stellar rotation. These SPI effects are informative for the study of the internal dynamics and atmospheric evolution of exoplanets. The nature of magnetic SPI is modeled to be strongly affected by both the stellar and planetary magnetic fields, possibly influencing the magnetic activity of both, as well as affecting the irradiation and even the migration of the planet and rotational evolution of the star. As phase-resolved observational techniques are applied to a large statistical sample of hot Jupiter systems, extensions to other tightly orbiting stellar systems, such as smaller planets close to M dwarfs become possible. In these systems, star-planet separations of tens of stellar radii begin to coincide with the radiative habitable zone where planetary magnetic fields are likely a necessary condition for surface habitability.Comment: Accepted for publication in the handbook of exoplanet

Learning and innovative elements of strategy adoption rules expand cooperative network topologies

Cooperation plays a key role in the evolution of complex systems. However, the level of cooperation extensively varies with the topology of agent networks in the widely used models of repeated games. Here we show that cooperation remains rather stable by applying the reinforcement learning strategy adoption rule, Q-learning on a variety of random, regular, small-word, scale-free and modular network models in repeated, multi-agent Prisoners Dilemma and Hawk-Dove games. Furthermore, we found that using the above model systems other long-term learning strategy adoption rules also promote cooperation, while introducing a low level of noise (as a model of innovation) to the strategy adoption rules makes the level of cooperation less dependent on the actual network topology. Our results demonstrate that long-term learning and random elements in the strategy adoption rules, when acting together, extend the range of network topologies enabling the development of cooperation at a wider range of costs and temptations. These results suggest that a balanced duo of learning and innovation may help to preserve cooperation during the re-organization of real-world networks, and may play a prominent role in the evolution of self-organizing, complex systems.Comment: 14 pages, 3 Figures + a Supplementary Material with 25 pages, 3 Tables, 12 Figures and 116 reference

Focused Deterrence and the Prevention of Violent Gun Injuries: Practice, Theoretical Principles, and Scientific Evidence

Focused deterrence strategies are a relatively new addition to a growing portfolio of evidence-based violent gun injury prevention practices available to policy makers and practitioners. These strategies seek to change offender behavior by understanding the underlying violence-producing dynamics and conditions that sustain recurring violent gun injury problems and by implementing a blended strategy of law enforcement, community mobilization, and social service actions. Consistent with documented public health practice, the focused deterrence approach identifies underlying risk factors and causes of recurring violent gun injury problems, develops tailored responses to these underlying conditions, and measures the impact of implemented interventions. This article reviews the practice, theoretical principles, and evaluation evidence on focused deterrence strategies. Although more rigorous randomized studies are needed, the available empirical evidence suggests that these strategies generate noteworthy gun violence reduction impacts and should be part of a broader portfolio of violence prevention strategies available to policy makers and practitioners

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone

Depressive Symptoms among Pregnant Women Screened in Obstetrics Settings

Objectives: This study aimed to describe the prevalence of depressive symptomatology during pregnancy when seen in obstetric settings, the extent of treatment in this population, and specific risk factors associated with mood symptoms in pregnancy. Methods: A total of 3472 pregnant women age 18 and older were screened while waiting for their prenatal care visits in 10 obstetrics clinics using a brief (10 minute) screening questionnaire. This screen measured demographics, tobacco and alcohol (TWEAK problem alcohol use screening measure), and depression measures, including the Center for Epidemiological Studies-Depression scale (CES-D), use of antidepressant medications, past history of depression, and current treatment (i.e., medications, psychotherapy, or counseling) for depression. Results: Of women screened, 20% (n = 689) scored above the cutoff score on the CES-D, and only 13.8% of those women reported receiving any formal treatment for depression. Past history of depression, poorer overall health, greater alcohol use consequences, smoking, being unmarried, unemployment, and lower educational attainment were significantly associated with symptoms of depression during pregnancy. Conclusions: These data show that a substantial number of pregnant women screened in obstetrics settings have significant symptoms of depression, and most of them are not being monitored in treatment during this vulnerable time. This information may be used to justify and streamline systematic screening for depression in clinical encounters with pregnant women as a first step in determining which women may require further treatment for their mood symptoms. As elevations in depressive symptomatology have been associated with adverse maternal and infant outcomes, further study of the impact of psychiatric treatment in gravid women is essential.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63218/1/154099903765448880.pd