Why don't I just throw it in the bin? - evaluation and self-esteem

Work in design and technology can provide a unique insight into quality through the process of evaluation. However, this is a two-edged sword in that evaluation can expose children's work to the perceived cold, hard light of public scrutiny. For many children at Key Stages 1 and 2, evaluation can be a daunting, high-risk enterprise due to a lack of self-esteem. Drawing upon case study evidence from work with children in schools, a number of strategies are proposed for children to develop a critical awareness of products and through this, a more confident approach to evaluating their designing and making. These include a graduation from evaluating familiar products made or produced by others, with a key emphasis on food, to evaluation of their own designing and making through the support of 'critical friends' within a group context. It is proposed that product evaluation should be a key feature of primary teaching, based upon regular, simple and brief whole class and group teaching sessions

Scrub Typhus in the Torres Strait Islands of North Queensland, Australia

Scrub typhus, caused by Orientia tsutsugamushi, occurs throughout Southeast Asia. We descript ten cases that occurred in the Torres Strait islands of northern Australia during 2000 and 2001. Preceding heavy rain may have contributed to the outbreak. The successful use of azithromycin in two pediatric patients is also reported

The Alleviate Advanced Pain Discovery Platform Data Hub:A national resource for accessing and sharing pain data

There are many clinical and non-clinical datasets investigating pain that have been collected by researchers over many years, however, finding and getting access to them is challenging. The data are siloed in hard-to-reach places, in non-standard formats, and it is not possible to assess how relevant they are before getting access. This is a barrier to the pain research community and results in duplication of effort. It does not have to be this way and there are alternative solutions available. Alleviate is an HDR UK Data Hub for the federated querying and secure sharing of UK pain data to researchers, analysts and clinicians at a national and international level. Alleviate is the Data Hub for the Advanced Pain Discovery Platform (APDP), a £24 million research initiative to break through the complexity of pain and reveal potential new treatment approaches to address a wide spectrum of chronic and debilitating clinical conditions

Phenotypic screen for oxygen consumption rate identifies an anti-cancer naphthoquinone that induces mitochondrial oxidative stress.

A hallmark of cancer cells is their ability to reprogram nutrient metabolism. Thus, disruption to this phenotype is a potential avenue for anti-cancer therapy. Herein we used a phenotypic chemical library screening approach to identify molecules that disrupted nutrient metabolism (by increasing cellular oxygen consumption rate) and were toxic to cancer cells. From this screen we discovered a 1,4-Naphthoquinone (referred to as BH10) that is toxic to a broad range of cancer cell types. BH10 has improved cancer-selective toxicity compared to doxorubicin, 17-AAG, vitamin K3, and other known anti-cancer quinones. BH10 increases glucose oxidation via both mitochondrial and pentose phosphate pathways, decreases glycolysis, lowers GSH:GSSG and NAPDH/NAPD+ ratios exclusively in cancer cells, and induces necrosis. BH10 targets mitochondrial redox defence as evidenced by increased mitochondrial peroxiredoxin 3 oxidation and decreased mitochondrial aconitase activity, without changes in markers of cytosolic or nuclear damage. Over-expression of mitochondria-targeted catalase protects cells from BH10-mediated toxicity, while the thioredoxin reductase inhibitor auranofin synergistically enhances BH10-induced peroxiredoxin 3 oxidation and cytotoxicity. Overall, BH10 represents a 1,4-Naphthoquinone with an improved cancer-selective cytotoxicity profile via its mitochondrial specificity

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

Mutations in ZMYND10, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms in Humans and Flies, Cause Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequencing in PCD-affected families afflicted with combined IDA and ODA defects, we found that 6/38 (16%) carried biallelic mutations in the conserved zinc-finger gene BLU (ZMYND10). ZMYND10 mutations conferred dynein-arm loss seen at the ultrastructural and immunofluorescence level and complete cilia immotility, except in hypomorphic p.Val16Gly (c.47T>G) homozygote individuals, whose cilia retained a stiff and slowed beat. In mice, Zmynd10 mRNA is restricted to regions containing motile cilia. In a Drosophila model of PCD, Zmynd10 is exclusively expressed in cells with motile cilia: chordotonal sensory neurons and sperm. In these cells, P-element-mediated gene silencing caused IDA and ODA defects, proprioception deficits, and sterility due to immotile sperm. Drosophila Zmynd10 with an equivalent c.47T>G (p.Val16Gly) missense change rescued mutant male sterility less than the wild-type did. Tagged Drosophila ZMYND10 is localized primarily to the cytoplasm, and human ZMYND10 interacts with LRRC6, another cytoplasmically localized protein altered in PCD. Using a fly model of PCD, we conclude that ZMYND10 is a cytoplasmic protein required for IDA and ODA assembly and that its variants cause ciliary dysmotility and PCD with laterality defects

Why don’t I just Throw it in the Bin? : Evaluation and Self-esteem

Work in design and technology can provide a unique insight into quality through the process of evaluation. However, this is a two-edged sword in that evaluation can expose children's work to the perceived cold, hard light of public scrutiny. For many children at Key Stages 1 and 2, evaluation can be a daunting, high-risk enterprise due to a lack of self-esteem. Drawing upon case study evidence from work with children in schools, a number of strategies are proposed for children to develop a critical awareness of products and through this, a more confident approach to evaluating their designing and making. These include a graduation from evaluating familiar products made or produced by others, with a key emphasis on food, to evaluation of their own designing and making through the support of 'critical friends' within a group context. It is proposed that product evaluation should be a key feature of primary teaching, based upon regular, simple and brief whole class and group teaching sessions.Peer reviewe