Parent training for preschool ADHD: a randomized controlled trial of specialized and generic programs

BackgroundThe New Forest Parenting Package' (NFPP), an 8-week home-based intervention for parents of preschoolers with attention-deficit/hyperactivity disorder (ADHD), fosters constructive parenting to target ADHD-related dysfunctions in attention and impulse control. Although NFPP has improved parent and laboratory measures of ADHD in community samples of children with ADHD-like problems, its efficacy in a clinical sample, and relative to an active treatment comparator, is unknown. The aims are to evaluate the short- and long-term efficacy and generalization effects of NFPP compared to an established clinic-based parenting intervention for treating noncompliant behavior [Helping the Noncompliant Child' (HNC)] in young children with ADHD. MethodsA randomized controlled trial with three parallel arms was the design for this study. A total of 164 3-4-year-olds, 73.8% male, meeting DSM-IV ADHD diagnostic criteria were randomized to NFPP (N=67), HNC (N=63), or wait-list control (WL, N=34). All participants were assessed at post-treatment. NFPP and HNC participants were assessed at follow-up in the next school year. Primary outcomes were ADHD ratings by teachers blind to and uninvolved in treatment, and by parents. Secondary ADHD outcomes included clinician assessments, and laboratory measures of on-task behavior and delay of gratification. Other outcomes included parent and teacher ratings of oppositional behavior, and parenting measures. (Trial name: Home-Based Parent Training in ADHD Preschoolers; Registry: ClinicalTrials.gov Identifier: NCT01320098; URL: ). ResultsIn both treatment groups, children's ADHD and ODD behaviors, as well as aspects of parenting, were rated improved by parents at the end of treatment compared to controls. Most of these gains in the children's behavior and in some parenting practices were sustained at follow-up. However, these parent-reported improvements were not corroborated by teacher ratings or objective observations. NFPP was not significantly better, and on a few outcomes significantly less effective, than HNC. ConclusionsThe results do not support the claim that NFPP addresses putative dysfunctions underlying ADHD, bringing about generalized change in ADHD, and its underpinning self-regulatory processes. The findings support documented difficulties in achieving generalization across nontargeted settings, and the importance of using blinded measures to provide meaningful assessments of treatment effects

Epistatic Interactions Alter Dynamics of Multilocus Gene-for-Gene Coevolution

Fitness costs associated with resistance or virulence genes are thought to play a key role in determining the dynamics of gene-for-gene (GFG) host-parasite coevolution. However, the nature of interactions between fitness effects of multiple resistance or virulence genes (epistasis) has received less attention. To examine effects of the functional form of epistasis on the dynamics of GFG host-parasite coevolution we modified a classic multilocus GFG model framework. We show that the type of epistasis between virulence genes largely determines coevolutionary dynamics, and that coevolutionary fluctuations are more likely with acceleratingly costly (negative) than with linear or deceleratingly costly (positive) epistasis. Our results demonstrate that the specific forms of interaction between multiple resistance or virulence genes are a crucial determinant of host-parasite coevolutionary dynamics

Core-collapse supernova progenitor constraints using the spatial distributions of massive stars in local galaxies

We study the spatial correlations between the H$\alpha$ emission and different types of massive stars in two local galaxies, the Large Magellanic Cloud (LMC) and Messier 33. We compare these to correlations derived for core-collapse supernovae (CCSNe) in the literature to connect CCSNe of different types with the initial masses of their progenitors and to test the validity of progenitor mass estimates which use the pixel statistics method. We obtain samples of evolved massive stars in both galaxies from catalogues with good spatial coverage and/or completeness, and combine them with coordinates of main-sequence stars in the LMC from the SIMBAD database. We calculate the spatial correlation of stars of different classes and spectral types with H$\alpha$ emission. We also investigate the effects of distance, noise and positional errors on the pixel statistics method. A higher correlation with H$\alpha$ emission is found to correspond to a shorter stellar lifespan, and we conclude that the method can be used as an indicator of the ages, and therefore initial masses, of SN progenitors. We find that the spatial distributions of type II-P SNe and red supergiants of appropriate initial mass ($\gtrsim$9 $M_{\odot}$) are consistent with each other. We also find the distributions of type Ic SNe and WN stars with initial masses $\gtrsim$20 $M_{\odot}$ consistent, while supergiants with initial masses around 15 $M_{\odot}$ are a better match for type IIb and II-L SNe. The type Ib distribution corresponds to the same stellar types as type II-P, which suggests an origin in interacting binaries. On the other hand, we find that luminous blue variable stars show a much stronger correlation with H$\alpha$ emission than do type IIn SNe.ERC, STF

Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity

Background: Immunotherapy has shown remarkable clinical promise in the treatment of various types of cancers. However, clinical benefits derive from a highly inflammatory mechanism of action. This presents unique challenges for use in pediatric brainstem tumors including diffuse intrinsic pontine glioma (DIPG), since treatment-related inflammation could cause catastrophic toxicity. Therefore, the goal of this study was to investigate whether inflammatory, immune-based therapies are likely to be too dangerous to pursue for the treatment of pediatric brainstem tumors. Methods: To complement previous immunotherapy studies using patient-derived xenografts in immunodeficient mice, we developed fully immunocompetent models of immunotherapy using transplantable, syngeneic tumors. These four models – HSVtk/GCV suicide gene immunotherapy, oncolytic viroimmunotherapy, adoptive T cell transfer, and CAR T cell therapy – have been optimized to treat tumors outside of the CNS and induce a broad spectrum of inflammatory profiles, maximizing the chances of observing brainstem toxicity. Results: All four models achieved anti-tumor efficacy in the absence of toxicity, with the exception of recombinant vaccinia virus expressing GMCSF, which demonstrated inflammatory toxicity. Histology, imaging, and flow cytometry confirmed the presence of brainstem inflammation in all models. Where used, the addition of immune checkpoint blockade did not introduce toxicity. Conclusions: It remains imperative to regard the brainstem with caution for immunotherapeutic intervention. Nonetheless, we show that further careful development of immunotherapies for pediatric brainstem tumors is warranted to harness the potential potency of anti-tumor immune responses, despite their possible toxicity within this anatomically sensitive location

A companion to a quasar at redshift 4.7

There is a growing consensus that the emergence of quasars at high redshifts is related to the onset of galaxy formation, suggesting that the detection of concentrations of gas accompanying such quasars should provide clues about the early history of galaxies. Quasar companions have been recently identified at redshifts up to $z \approx 3$. Here we report observations of Lyman-$\alpha$ emission (a tracer of ionised hydrogen) from the companion to a quasar at $z$=4.702, corresponding to a time when the Universe was less than ten per cent of its present age. We argue that most of the emission arises in a gaseous nebula that has been photoionised by the quasar, but an additional component of continuum light -perhaps quasar light scattered from dust in the companion body, or emission from young stars within the nebula- appears necessary to explain the observations. These observations may be indicative of the first stages in the assembly of galaxy-sized structures.Comment: 8 pages, 4 figures, plain LaTeX. Accepted for publication in Natur

Comparison and Mapping Facilitate Relation Discovery and Predication

Relational concepts play a central role in human perception and cognition, but little is known about how they are acquired. For example, how do we come to understand that physical force is a higher-order multiplicative relation between mass and acceleration, or that two circles are the same-shape in the same way that two squares are? A recent model of relational learning, DORA (Discovery of Relations by Analogy; Doumas, Hummel & Sandhofer, 2008), predicts that comparison and analogical mapping play a central role in the discovery and predication of novel higher-order relations. We report two experiments testing and confirming this prediction

Neo-Aristotelian Naturalism and the Evolutionary Objection: Rethinking the Relevance of Empirical Science

Neo-Aristotelian metaethical naturalism is a modern attempt at naturalizing ethics using ideas from Aristotle’s teleological metaphysics. Proponents of this view argue that moral virtue in human beings is an instance of natural goodness, a kind of goodness supposedly also found in the realm of non-human living things. Many critics question whether neo-Aristotelian naturalism is tenable in light of modern evolutionary biology. Two influential lines of objection have appealed to an evolutionary understanding of human nature and natural teleology to argue against this view. In this paper, I offer a reconstruction of these two seemingly different lines of objection as raising instances of the same dilemma, giving neo-Aristotelians a choice between contradicting our considered moral judgment and abandoning metaethical naturalism. I argue that resolving the dilemma requires showing a particular kind of continuity between the norms of moral virtue and norms that are necessary for understanding non-human living things. I also argue that in order to show such a continuity, neo-Aristotelians need to revise the relationship they adopt with empirical science and acknowledge that the latter is relevant to assessing their central commitments regarding living things. Finally, I argue that to move this debate forward, both neo-Aristotelians and their critics should pay attention to recent work on the concept of organism in evolutionary and developmental biology