Susceptibility sets and the final outcome of collective Reed–Frost epidemics

This paper is concerned with exact results for the final outcome of stochastic SIR (susceptible → infective → recovered) epidemics among a closed, finite and homogeneously mixing population. The factorial moments of the number of initial susceptibles who ultimately avoid infection by such an epidemic are shown to be intimately related to the concept of a susceptibility set. This connection leads to simple, probabilistically illuminating proofs of exact results concerning the total size and severity of collective Reed–Frost epidemic processes, in terms of Gontcharoff polynomials, first obtained in a series of papers by Claude Lef`evre and Philippe Picard. The proofs extend easily to include general final state random variables defined on SIR epidemics, and also to multitype epidemics

The DCDC2 deletion is not a risk factor for dyslexia

Dyslexia is a specific impairment in learning to read and has strong heritability. An intronic deletion within the DCDC2 gene, with ~8% frequency in European populations, is increasingly used as a marker for dyslexia in neuroimaging and behavioral studies. At a mechanistic level, this deletion has been proposed to influence sensory processing capacity, and in particular sensitivity to visual coherent motion. Our re-assessment of the literature, however, did not reveal strong support for a role of this specific deletion in dyslexia. We also analyzed data from five distinct cohorts, enriched for individuals with dyslexia, and did not identify any signal indicative of associations for the DCDC2 deletion with reading-related measures, including in a combined sample analysis (N=526). We believe we conducted the first replication analysis for a proposed deletion effect on visual motion perception and found no association (N=445 siblings). We also report that the DCDC2 deletion has a frequency of 37.6% in a cohort representative of the general population recruited in Hong Kong (N=220). This figure, together with a lack of association between the deletion and reading abilities in this cohort, indicates the low likelihood of a direct deletion effect on reading skills. Therefore, on the basis of multiple strands of evidence, we conclude that the DCDC2 deletion is not a strong risk factor for dyslexia. Our analyses and literature re-evaluation are important for interpreting current developments within multidisciplinary studies of dyslexia and, more generally, contribute to current discussions about the importance of reproducibility in science

Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

Background - Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods - We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results - We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions - A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits

Policy failure and the policy-implementation gap: can policy support programs help?

There is an increasing awareness that policies do not succeed or fail on their own merits. Within complex messy systems, it is unclear how best to ensure effective policy design and implementation. However, rather than just let policies drift into full or even partial failure, governments are now beginning to take an interest in ways in which the policy process – especially the implementation phase – can be strengthened and supported. This article contributes to the debate in three ways: by unpicking the key factors behind policy failure; by exploring different approaches to policy support; and by identifying key messages for policy practitioners

Effects of school-based interventions on mental health stigmatization: a systematic review

Stigmatizing, or discriminatory, perspectives and behaviour, which target individuals on the basis of their mental health, are observed in even the youngest school children. We conducted a systematic review of the published and unpublished, scientific literature concerning the benefits and harms of school-based interventions, which were directed at students 18 years of age or younger to prevent or eliminate such stigmatization. Forty relevant studies were identified, yet only a qualitative synthesis was deemed appropriate. Five limitations within the evidence base constituted barriers to drawing conclusive inferences about the effectiveness and harms of school-based interventions: poor reporting quality, a dearth of randomized controlled trial evidence, poor methods quality for all research designs, considerable clinical heterogeneity, and inconsistent or null results. Nevertheless, certain suggestive evidence derived both from within and beyond our evidence base has allowed us to recommend the development, implementation and evaluation of a curriculum, which fosters the development of empathy and, in turn, an orientation toward social inclusion and inclusiveness. These effects may be achieved largely by bringing especially but not exclusively the youngest children into direct, structured contact with an infant, and likely only the oldest children and youth into direct contact with individuals experiencing mental health difficulties. The possible value of using educational activities, materials and contents to enhance hypothesized benefits accruing to direct contact also requires investigation. Overall, the curriculum might serve as primary prevention for some students and as secondary prevention for others

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases