Reviewing, indicating, and counting books for modern research evaluation systems

In this chapter, we focus on the specialists who have helped to improve the conditions for book assessments in research evaluation exercises, with empirically based data and insights supporting their greater integration. Our review highlights the research carried out by four types of expert communities, referred to as the monitors, the subject classifiers, the indexers and the indicator constructionists. Many challenges lie ahead for scholars affiliated with these communities, particularly the latter three. By acknowledging their unique, yet interrelated roles, we show where the greatest potential is for both quantitative and qualitative indicator advancements in book-inclusive evaluation systems.Comment: Forthcoming in Glanzel, W., Moed, H.F., Schmoch U., Thelwall, M. (2018). Springer Handbook of Science and Technology Indicators. Springer Some corrections made in subsection 'Publisher prestige or quality

Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency. RESULTS: We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies. These variants were more frequent in high-flow than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM models that recapitulated the human phenotype validated the pathogenesis of the mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF inhibitor vemurafinib restored blood flow in AVM. CONCLUSION: Our findings uncover a major cause of sporadic VMs of different clinical types and thereby offer the potential of personalized medical treatment by repurposing existing licensed cancer therapies. FUNDING: This work was funded or supported by grants from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma Research Alliance, the European Research Council, and the National Human Genome Research Institute (US)

Assessment of sleep-related disorders in children with sickle cell disease

Sleep-related disorders (SRDs) are common in sickle cell disease, however, identification may be time-consuming. Simultaneous survey of multiple SRDs utilizing a simplified instrument would facilitate screening. A simplified questionnaire investigating SRDs [sleep-disordered breathing (SDB), restless legs syndrome (RLS), insomnia, parasomnias, and daytime effects of disrupted sleep] was administered to 2-18-year-old children with sickle cell disease. One hundred participants completed this 5-7 minute survey without difficulties: 54 awoke unrefreshed, 41 had short-term insomnia, 30 had sleep-maintenance insomnia, 21 had chronic sleep-onset insomnia, 54 had chronic habitual snoring and 11 met the criteria for RLS. Sleep-maintenance insomnia was associated with increased body mass index (BMI) (p = 0.001), and chronic sleep-onset insomnia was associated with higher hemoglobin (Hb) levels (p = 0.04). Survey-reported symptoms of SRDs were significantly higher than that reported in the general pediatric population. A fast and simplified SRD survey is feasible and suggests a high prevalence of SRDs in children with sickle cell disease