Behavioural and Developmental Interventions for Autism Spectrum Disorder: A Clinical Systematic Review

Background: Much controversy exists regarding the clinical efficacy of behavioural and developmental interventions for improving the core symptoms of autism spectrum disorders (ASD). We conducted a systematic review to summarize the evidence on the effectiveness of behavioural and developmental interventions for ASD. Methods and Findings: Comprehensive searches were conducted in 22 electronic databases through May 2007. Further information was obtained through hand searching journals, searching reference lists, databases of theses and dissertations, and contacting experts in the field. Experimental and observational analytic studies were included if they were written in English and reported the efficacy of any behavioural or developmental intervention for individuals with ASD. Two independent reviewers made the final study selection, extracted data, and reached consensus on study quality. Results were summarized descriptively and, where possible, meta-analyses of the study results were conducted. One-hundred-and-one studies at predominantly high risk of bias that reported inconsistent results across various interventions were included in the review. Meta-analyses of three controlled clinical trials showed that Lovaas treatment was superior to special education on measures of adaptive behaviour, communication and interaction, comprehensive language, daily living skills, expressive language, overall intellectual functioning and socialization. High-intensity Lovaas was superior to low-intensity Lovaas on measures of intellectual functioning in two retrospective cohort studies. Pooling the results of two randomized controlle

Replication foci dynamics: replication patterns are modulated by S-phase checkpoint kinases in fission yeast

Although the molecular enzymology of DNA replication is well characterised, how and why it occurs in discrete nuclear foci is unclear. Using fission yeast, we show that replication takes place in a limited number of replication foci, whose distribution changes with progression through S phase. These sites define replication factories which contain on average 14 replication forks. We show for the first time that entire foci are mobile, able both to fuse and re-segregate. These foci form distinguishable patterns during S phase, whose succession is reproducible, defining early-, mid- and late-S phase. In wild-type cells, this same temporal sequence can be detected in the presence of hydroxyurea (HU), despite the reduced rate of replication. In cells lacking the intra-S checkpoint kinase Cds1, replication factories dismantle on HU. Intriguingly, even in the absence of DNA damage, the replication foci in cds1 cells assume a novel distribution that is not present in wild-type cells, arguing that Cds1 kinase activity contributes to the spatio-temporal organisation of replication during normal cell growth

Steps toward determination of the size and structure of the broad-line region in active galactic nuclei. IX. Ultraviolet observations of fairall

An 8 month monitoring campaign on the Seyfert 1 galaxy Fairall 9 has been conducted with the International Ultraviolet Explorer in an attempt to obtain reliable estimates of continuum-continuum and continuum-emission-line delays for a high-luminosity active galactic nucleus (AGN). While the results of this campaign are more ambiguous than those of previous monitoring campaigns on lower luminosity sources, we find general agreement with the earlier results: (1) there is no measurable lag between ultraviolet continuum bands, and (2) the measured emission-line time lags are very short. It is especially notable that the Lyα + N v emission-line lag is about 1 order of magnitude smaller than determined from a previous campaign by Clavel, Wamsteker, & Glass (1989) when Fairall 9 was in a more luminous state. In other well-monitored sources, specifically NGC 5548 and NGC 3783, the highest ionization lines are found to respond to continuum variations more rapidly than the lower ionization lines, which suggests a radially ionization-stratified broad-line region. In this case, the results are less certain, since none of the emission-line lags are very well determined. The best-determined emission line lag is Lyα + N v, for which we find that the centroid of the continuum-emission-line cross-correlation function is τcent ≈ 14-20 days. We measure a lag τcent ≲ 4 days for He II λ1640; this result is consistent with the ionization-stratification pattern seen in lower luminosity sources, but the relatively large uncertainties in the emission-line lags measured here cannot rule out similar lags for Lyα + N v and He II λ1640 at a high level of significance. We are unable to determine a reliable lag for C IV λ1550, but we note that the profiles of the variable parts of Lyα and C IV λ1550 are not the same, which does not support the hypothesis that the strongest variations in these two lines arise in the same region

Spatial regulation and organization of DNA replication within the nucleus

Duplication of chromosomal DNA is a temporally and spatially regulated process. The timing of DNA replication initiation at various origins is highly coordinated; some origins fire early and others late during S phase. Moreover, inside the nuclei, the bulk of DNA replication is physically organized in replication factories, consisting of DNA polymerases and other replication proteins. In this review article, we discuss how DNA replication is organized and regulated spatially within the nucleus and how this spatial organization is linked to temporal regulation. We focus on DNA replication in budding yeast and fission yeast and, where applicable, compare yeast DNA replication with that in bacteria and metazoans