What you know can influence what you are going to know (especially for older adults)

Stimuli related to an individual's knowledge/experience are often more memorable than abstract stimuli, particularly for older adults. This has been found when material that is congruent with knowledge is contrasted with material that is incongruent with knowledge, but there is little research on a possible graded effect of congruency. The present study manipulated the degree of congruency of study material with participants’ knowledge. Young and older participants associated two famous names to nonfamous faces, where the similarity between the nonfamous faces and the real famous individuals varied. These associations were incrementally easier to remember as the name-face combinations became more congruent with prior knowledge, demonstrating a graded congruency effect, as opposed to an effect based simply on the presence or absence of associations to prior knowledge. Older adults tended to show greater susceptibility to the effect than young adults, with a significant age difference for extreme stimuli, in line with previous literature showing that schematic support in memory tasks particularly benefits older adults

Anthrax Toxins Inhibit Neutrophil Signaling Pathways in Brain Endothelium and Contribute to the Pathogenesis of Meningitis

Anthrax meningitis is the main neurological complication of systemic infection with Bacillus anthracis approaching 100% mortality. The presence of bacilli in brain autopsies indicates that vegetative bacteria are able to breach the blood-brain barrier (BBB). The BBB represents not only a physical barrier but has been shown to play an active role in initiating a specific innate immune response that recruits neutrophils to the site of infection. Currently, the basic pathogenic mechanisms by which B. anthracis penetrates the BBB and causes anthrax meningitis are poorly understood.Using an in vitro BBB model, we show for the first time that B. anthracis efficiently invades human brain microvascular endothelial cells (hBMEC), the single cell layer that comprises the BBB. Furthermore, transcriptional profiling of hBMEC during infection with B. anthracis revealed downregulation of 270 (87%) genes, specifically key neutrophil chemoattractants IL-8, CXCL1 (Gro alpha) and CXCL2 (Gro beta), thereby strongly contrasting hBMEC responses observed with other meningeal pathogens. Further studies using specific anthrax toxin-mutants, quantitative RT-PCR, ELISA and in vivo assays indicated that anthrax toxins actively suppress chemokine production and neutrophil recruitment during infection, allowing unrestricted proliferation and dissemination of the bacteria. Finally, mice challenged with B. anthracis Sterne, but not the toxin-deficient strain, developed meningitis.These results suggest a significant role for anthrax toxins in thwarting the BBB innate defense response promoting penetration of bacteria into the central nervous system. Furthermore, establishment of a mouse model for anthrax meningitis will aid in our understanding of disease pathogenesis and development of more effective treatment strategies

Understanding implementation processes of clinical pathways and clinical practice guidelines in pediatric contexts: a study protocol

<p>Abstract</p> <p>Background</p> <p>Canada is among the most prosperous nations in the world, yet the health and wellness outcomes of Canadian children are surprisingly poor. There is some evidence to suggest that these poor health outcomes are partly due to clinical practice variation, which can stem from failure to apply the best available research evidence in clinical practice, otherwise known as knowledge translation (KT). Surprisingly, clinical practice variation, even for common acute paediatric conditions, is pervasive. Clinical practice variation results in unnecessary medical treatments, increased suffering, and increased healthcare costs. This study focuses on improving health outcomes for common paediatric acute health concerns by evaluating strategies that improve KT and reduce clinical practice variation.</p> <p>Design/Methods</p> <p>Using a multiple case study design, qualitative and quantitative data will be collected from four emergency departments in western Canada. Data sources will include: pre- and post-implementation focus group data from multidisciplinary healthcare professionals; individual interviews with the local champions, KT intervention providers, and unit/site leaders/managers; Alberta Context Tool (ACT) survey data; and aggregated patient outcome data. Qualitative and quantitative data will be systematically triangulated, and matrices will be built to do cross-case comparison. Explanations will be built about the success or lack of success of the clinical practice guidelines (CPG) and clinical pathways (CPs) uptake based upon the cross-case comparisons.</p> <p>Significance</p> <p>This study will generate new knowledge about the potential causal mechanisms and factors which shape implementation. Future studies will track the impact of the CPG/CPs implementation on children's health outcome, and healthcare costs.</p

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe