Generation of mice with a conditional Foxp2 null allele

Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12–14 of Foxp2; these exons encode the DNA-binding motif, a key functional domain. We demonstrate that early global Cre-mediated recombination yields a null allele, as shown by loss of the loxP-flanked exons at the RNA level and an absence of Foxp2 protein. Homozygous null mice display severe motor impairment, cerebellar abnormalities and early postnatal lethality, consistent with other Foxp2 mutants. When crossed to transgenic lines expressing Cre protein in a spatially and/or temporally controlled manner, these conditional mice will provide new insights into the contributions of Foxp2 to distinct neural circuits, and allow dissection of roles during development and in the mature brain. genesis 45:440–446, 2007. Published 2007 Wiley-Liss, Inc

Population effectiveness of the pentavalent and monovalent rotavirus vaccines: a systematic review and meta-analysis of observational studies

Abstract Background Rotavirus was the leading cause of acute gastroenteritis (AGE) in infants and young children prior to the introduction of routine vaccination. Since 2006 there have been two licensed vaccines available; with successful clinical trials leading the World Health Organization to recommend rotavirus vaccination for all children worldwide. In order to inform immunisation policy we have conducted a systematic review and meta-analysis of observation studies to assess population effectiveness against acute gastroenteritis. Methods We systematically searched PubMed, Medline, Web of Science, Cinhal and Academic Search Premier and grey literature sources for studies published between January 2006 and April 2014. Studies were eligible for inclusion if they were observational measuring population effectiveness of rotavirus vaccination against health care attendances for rotavirus gastroenteritis or AGE. To evaluate study quality we use used the Newcastle-Ottawa Scale for non-randomised studies, categorising studies by risk of bias. Publication bias was assessed using funnel plots. If two or more studies reported a measure of vaccine effectiveness (VE), we conducted a random effects meta-analysis. We stratified analyses by World Bank country income level and used study quality in sensitivity analyses. Results We identified 30 studies, 19 were from high-income countries and 11 from middle-income countries. Vaccine effectiveness against hospitalization for laboratory confirmed rotavirus gastroenteritis was highest in high-income countries (89% VE; 95% CI 84-92%) compared to middle-income countries (74% VE; 95% CI 67-80%). Vaccine effectiveness was higher for those receiving the complete vaccine schedule (81% VE; 95% CI 75-86%) compared to partial schedule (62% VE; 95% CI 55-69%). Two studies from high-income countries measured VE against community consultations for AGE with a pooled estimate of 40% (95% CI 13-58%; 2 studies). Conclusions We found strong evidence to further support the continued use of rotavirus vaccines. Vaccine effectiveness was similar to that reported in clinical trials for both high and middle-income countries. There is limited data from Low income settings at present. There was lower effectiveness against milder disease. Further studies, should continue to report effectiveness against AGE and less-severe rotavirus disease because as evidenced by pre-vaccine introduction studies this is likely to contribute the greatest burden on healthcare resources, particularly in high-income countries

Metrology and quality assurance from surveillance of gas compositions over PuO[sub 2]

Until the late 1980s, a primary mission of the Department of Energy (DOE) has been the production of nuclear materials for nuclear weapons. Termination of the Cold War in 1989 and the subsequent nuclear weapons treaties dramatically decreased the inventory needs for nuclear weapons. These activities resulted in the consolidation of nuclear material inventories and activities, generating substantial amounts of surplus nuclear materials ranging from plutonium metal and pure oxides to impure plutonium residues. Packaging and storage of these materials in physically and environmentally safe configurations for significant time periods were required. In 1993 the Defense Nuclear Facility Safety Board (DNFSB) and the DOE Office of Nuclear Safety examined the storage of metal and oxides at the Rocky Flats Plant that ultimately resulted in recommendation 94-1, calling for a standard to define the processing and storage of plutonium bearing materials. This recommendation generated a standard for storage of plutonium metals and oxides, DOE-STD-3013-2000, which is now in its fourth revision. The current DOE 3013 Standard is limited to metal and oxides, which contain greater than 30 weight percent plutonium and uranium. The 3013 Standard requires that the oxide be calcined to 950 C for two hours in an oxidizing environment. Before packaging, the oxide is required to have less than 0.5 weight percent moisture. Up to five kilograms of the stabilized oxide material is subsequently sealed in a set of two-nested welded stainless steel container, which must have a power less than 19 Watts

Early-onset Amyloid Deposition and Cognitive Deficits in Transgenic Mice Expressing a Double Mutant Form of Amyloid Precursor Protein 695

n/

Integrating acute stroke telemedicine consultations into specialists' usual practice: a qualitative analysis comparing the experience of Australia and the United Kingdom

Stroke telemedicine can reduce healthcare inequities by increasing access to specialists. Successful telemedicine networks require specialists adapting clinical practice to provide remote consultations. Variation in experiences of specialists between different countries is unknown. To support future implementation, we compared perceptions of Australian and United Kingdom specialists providing remote acute stroke consultations. Specialist participants were identified using purposive sampling from two new services: Australia's Victorian Stroke Telemedicine Program (n = 6; 2010-13) and the United Kingdom's Cumbria and Lancashire telestroke network (n = 5; 2010-2012). Semi-structured interviews were conducted pre- and post-implementation, recorded and transcribed verbatim. Deductive thematic and content analysis (NVivo) was undertaken by two independent coders using Normalisation Process Theory to explore integration of telemedicine into practice. Agreement between coders was M = 91%, SD = 9 and weighted average κ = 0.70. Cross-cultural similarities and differences were found. In both countries, specialists described old and new consulting practices, the purpose and value of telemedicine systems, and concerns regarding confidence in the assessment and diagnostic skills of unknown colleagues requesting telemedicine support. Australian specialists discussed how remote consultations impacted on usual roles and suggested future improvements, while United Kingdom specialists discussed system governance, policy and procedures. Australian and United Kingdom specialists reported telemedicine required changes in work practice and development of new skills. Both groups described potential for improvements in stroke telemedicine systems with Australian specialists more focused on role change and the United Kingdom on system governance issues. Future research should examine if cross-cultural variation reflects different models of care and extends to other networks

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Judgment of the Humanness of an Interlocutor Is in the Eye of the Beholder

Despite tremendous advances in artificial language synthesis, no machine has so far succeeded in deceiving a human. Most research focused on analyzing the behavior of “good” machine. We here choose an opposite strategy, by analyzing the behavior of “bad” humans, i.e., humans perceived as machine. The Loebner Prize in Artificial Intelligence features humans and artificial agents trying to convince judges on their humanness via computer-mediated communication. Using this setting as a model, we investigated here whether the linguistic behavior of human subjects perceived as non-human would enable us to identify some of the core parameters involved in the judgment of an agents' humanness. We analyzed descriptive and semantic aspects of dialogues in which subjects succeeded or failed to convince judges of their humanness. Using cognitive and emotional dimensions in a global behavioral characterization, we demonstrate important differences in the patterns of behavioral expressiveness of the judges whether they perceived their interlocutor as being human or machine. Furthermore, the indicators of interest displayed by the judges were predictive of the final judgment of humanness. Thus, we show that the judgment of an interlocutor's humanness during a social interaction depends not only on his behavior, but also on the judge himself. Our results thus demonstrate that the judgment of humanness is in the eye of the beholder