A lake's life is not its own

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62504/1/408149a0.pd

The size-brightness correspondence:evidence for crosstalk among aligned conceptual feature dimensions

The same core set of cross-sensory correspondences connecting stimulus features across different sensory channels are observed regardless of the modality of the stimulus with which the correspondences are probed. This observation suggests that correspondences involve modality-independent representations of aligned conceptual feature dimensions, and predicts a size-brightness correspondence, in which smaller is aligned with brighter. This suggestion accommodates cross-sensory congruity effects where contrasting feature values are specified verbally rather than perceptually (e.g., where the words WHITE and BLACK interact with the classification of high and low pitch sounds). Experiment 1 brings these two issues together in assessing a conceptual basis for correspondences. The names of bright/white and dark/black substances were presented in a speeded brightness classification task in which the two alternative response keys differed in size. A size-brightness congruity effect was confirmed, with substance names classified more quickly when the relative size of the response key needing to be pressed was congruent with the brightness of the named substance (e.g., when yoghurt was classified as a bright substance by pressing the smaller of two keys). Experiment 2 assesses the proposed conceptual basis for this congruity effect by requiring the same named substances to be classified according to their edibility (with all of the bright/dark substances having been selected for their edibility/inedibility, respectively). The predicted absence of a size-brightness congruity effect, along with other aspects of the results, supports the proposed conceptual basis for correspondences and speaks against accounts in which modality-specific perceptuomotor representations are entirely responsible for correspondence-induced congruity effects

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. / METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). / RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low–molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). / CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. / FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research

Conducting retrospective impact analysis to inform a medical research charity’s funding strategies: The case of Asthma UK

© 2013 Hanney et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. METHODS: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the ‘Centre’) which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. RESULTS: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthma-related clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. CONCLUSIONS: We systematically demonstrate that all types of Asthma UK’s research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study’s findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact.This study was funded by Asthma UK

Timing the initiation of multiple myeloma

The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2nd-3rd decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

Amyloid associated with elastin-staining laminar aggregates in the lungs of patients diagnosed with acute respiratory distress syndrome

BACKGROUND: The heterogeneity of conditions underlying respiratory distress, whether classified clinically as acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS), has hampered efforts to identify and more successfully treat these patients. Examination of postmortem lungs among cases clinically diagnosed as ARDS identified a cohort that showed a consistent morphology at the light and electron microscope levels, and featured pathognomonic structures which we termed elastin-staining laminar structures (ELS). METHODS: Postmortem tissues were stained using the Verhoeff-Van Gieson procedure for elastic fibers, and with Congo red for examination under a polarizing microscope. Similar samples were examined by transmission EM. RESULTS: The pathognomonic ELS presented as ordered molecular aggregates when stained using the Verhoeff-van Gieson technique for elastic fibers. In several postmortem lungs, the ELS also displayed apple-green birefringence after staining with Congo red, suggesting the presence of amyloid. Remarkably, most of the postmortem lungs with ELS exhibited no significant acute inflammatory cellular response such as neutrophilic reaction, and little evidence of widespread edema except for focal intra-alveolar hemorrhage. CONCLUSIONS: Postmortem lungs that exhibit the ELS constitute a morphologically-identifiable subgroup of ARDS cases. The ordered nature of the ELS, as indicated by both elastin and amyloid stains, together with little morphological evidence of inflammation or edema, suggests that this cohort of ARDS may represent another form of conformational disease. If this hypothesis is confirmed, it will require a new approach in the diagnosis and treatment of patients who exhibit this form of acute lung injury