Service engagement in interventions for street-connected children and young people: a summary of evidence supplementing a recent Cochrane–Campbell review

Abstract Background This paper builds on a Cochrane–Campbell systematic review of interventions that reduce harms and promote reintegration in street-connected children and young people focusing on intervention outcomes. The aim of the present analysis is to explore questions raised in the systematic review over the potential role of service engagement in mediating outcomes of relevant interventions. Objective The paper summarises engagement-related findings from quantitative intervention evaluations with street-connected populations of children and young people, as reported by study authors. It seeks to contribute to theoretical and methodological understandings of service engagement with street-connected youth populations and to highlight gaps in current knowledge. Methods Drawing on the original search for the Cochrane–Campbell review, we rescreened search results in our database and included quantitative findings if relevant to our current research questions, regardless of study design. Additionally, we sought new study publications from authors whose work was included in the original systematic review. The discussion explores relevant data from five studies included in the original systematic review, ten studies excluded from the review, and two studies published after the completion of the review. Results The measures of service engagement in the included studies focused on treatment attendance, ‘level of engagement’, and service satisfaction. Evidence on the impact of service engagement on other outcomes in interventions for street-connected children and young people was limited. Available data on the predictors and impact of service engagement were mixed and appear not to provide robust support for common hypotheses in the relevant context

Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.

The somatic mutations in a cancer genome are the aggregate outcome of one or more mutational processes operative through the lifetime of the individual with cancer. Each mutational process leaves a characteristic mutational signature determined by the mechanisms of DNA damage and repair that constitute it. A role was recently proposed for the APOBEC family of cytidine deaminases in generating particular genome-wide mutational signatures and a signature of localized hypermutation called kataegis. A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B, has been associated with modestly increased risk of breast cancer. Here we show that breast cancers in carriers of the deletion show more mutations of the putative APOBEC-dependent genome-wide signatures than cancers in non-carriers. The results suggest that the APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes, although the mechanism by which this increase in activity occurs remains unknown.We would like to thank the Wellcome Trust for support (grant reference 098051). SN-Z is a Wellcome-Beit Prize Fellow and is supported through a Wellcome Trust Intermediate Fellowship (grant reference WT100183MA). PJC is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant reference WT088340MA). NB is an EHA fellow and is supported by a Lady Tata Memorial Trust award. The H.L. Holmes Award from the National Research Council Canada and an EMBO Fellowship supports AS

Infantile Convulsions with Paroxysmal Dyskinesia (ICCA Syndrome) and Copy Number Variation at Human Chromosome 16p11

BACKGROUND: Benign infantile convulsions and paroxysmal dyskinesia are episodic cerebral disorders that can share common genetic bases. They can be co-inherited as one single autosomal dominant trait (ICCA syndrome); the disease ICCA gene maps at chromosome 16p12-q12. Despite intensive and conventional mutation screening, the ICCA gene remains unknown to date. The critical area displays highly complicated genomic architecture and is the site of deletions and duplications associated with various diseases. The possibility that the ICCA syndrome is related to the existence of large-scale genomic alterations was addressed in the present study. METHODOLOGY/PRINCIPAL FINDINGS: A combination of whole genome and dedicated oligonucleotide array comparative genomic hybridization coupled with quantitative polymerase chain reaction was used. Low copy number of a region corresponding to a genomic variant (Variation_7105) located at 16p11 nearby the centromere was detected with statistical significance at much higher frequency in patients from ICCA families than in ethnically matched controls. The genomic variant showed no apparent difference in size and copy number between patients and controls, making it very unlikely that the genomic alteration detected here is ICCA-specific. Furthermore, no other genomic alteration that would directly cause the ICCA syndrome in those nine families was detected in the ICCA critical area. CONCLUSIONS/SIGNIFICANCE: Our data excluded that inherited genomic deletion or duplication events directly cause the ICCA syndrome; rather, they help narrowing down the critical ICCA region dramatically and indicate that the disease ICCA genetic defect lies very close to or within Variation_7105 and hence should now be searched in the corresponding genomic area and its surrounding regions

A framework for teaching epistemic insight in schools

This paper gives the rationale and a draft outline for a framework for education to teach epistemic insight into schools in England. The motivation to research and propose a strategy to teach and assess epistemic insight followed research that investigated how students and teachers in primary and secondary schools respond to big questions about the nature of reality and human personhood. The research revealed that there are pressures in schools that dampen students’ expressed curiosity in these types of questions and limit their developing epistemic insight into how science, religion and the wider humanities relate. These findings prompted the construction of a framework for education for students aged 5–16 designed to encourage students’ expressed interest in big questions and develop their understanding of the ways that science interacts with other ways of knowing. The centrepiece of the framework is a sequence of learning objectives for epistemic insight, organised into three categories. The categories are, firstly, the nature of science in real world contexts and multidisciplinary arenas; secondly, ways of knowing and how they interact; and thirdly, the relationships between science and religion. Our current version of the Framework is constructed to respond to the way that teaching is organised in England. The key principles and many of the activities could be adopted and tailored to work in many other countries

Positional Cues in the Drosophila Nerve Cord: Semaphorins Pattern the Dorso-Ventral Axis

Positional cues target sensory axons to appropriate volumes of the developing nervous system independently of their synaptic partners

How Large Is the Metabolome? A Critical Analysis of Data Exchange Practices in Chemistry

Calculating the metabolome size of species by genome-guided reconstruction of metabolic pathways misses all products from orphan genes and from enzymes lacking annotated genes. Hence, metabolomes need to be determined experimentally. Annotations by mass spectrometry would greatly benefit if peer-reviewed public databases could be queried to compile target lists of structures that already have been reported for a given species. We detail current obstacles to compile such a knowledge base of metabolites.As an example, results are presented for rice. Two rice (oryza sativa) subspecies have been fully sequenced, oryza japonica and oryza indica. Several major small molecule databases were compared for listing known rice metabolites comprising PubChem, Chemical Abstracts, Beilstein, Patent databases, Dictionary of Natural Products, SetupX/BinBase, KNApSAcK DB, and finally those databases which were obtained by computational approaches, i.e. RiceCyc, KEGG, and Reactome. More than 5,000 small molecules were retrieved when searching these databases. Unfortunately, most often, genuine rice metabolites were retrieved together with non-metabolite database entries such as pesticides. Overlaps from database compound lists were very difficult to compare because structures were either not encoded in machine-readable format or because compound identifiers were not cross-referenced between databases.We conclude that present databases are not capable of comprehensively retrieving all known metabolites. Metabolome lists are yet mostly restricted to genome-reconstructed pathways. We suggest that providers of (bio)chemical databases enrich their database identifiers to PubChem IDs and InChIKeys to enable cross-database queries. In addition, peer-reviewed journal repositories need to mandate submission of structures and spectra in machine readable format to allow automated semantic annotation of articles containing chemical structures. Such changes in publication standards and database architectures will enable researchers to compile current knowledge about the metabolome of species, which may extend to derived information such as spectral libraries, organ-specific metabolites, and cross-study comparisons

Identification of Copy Number Variants Defining Genomic Differences among Major Human Groups

BACKGROUND:Understanding the genetic contribution to phenotype variation of human groups is necessary to elucidate differences in disease predisposition and response to pharmaceutical treatments in different human populations. METHODOLOGY/PRINCIPAL FINDINGS:We have investigated the genome-wide profile of structural variation on pooled samples from the three populations studied in the HapMap project by comparative genome hybridization (CGH) in different array platforms. We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other. Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space) within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs) translate into gene-expression differences among populations, suggesting that they could have functional consequences. In addition, the identification of single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium with the copy number alleles allowed us to detect evidences of population differentiation and recent selection at the nucleotide variation level. CONCLUSIONS:Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies