The management of non-valvular atrial fibrillation (NVAF) in Australian general practice: bridging the evidence-practice gap. A national, representative postal survey

<p>Abstract</p> <p>Background</p> <p>General practitioners (GPs) are ideally placed to bridge the widely noted evidence-practice gap between current management of NVAF and the need to increase anticoagulant use to reduce the risk of fatal and disabling stroke in NVAF. We aimed to identify gaps in current care, and asked GPs to identify potentially useful strategies to overcome barriers to best practice.</p> <p>Methods</p> <p>We obtained contact details for a random sample of 1000 GPs from a national commercial data-base. Randomly selected GPs were mailed a questionnaire after an advance letter. Standardised reminders were administered to enhance response rates. As part of a larger survey assessing GP management of NVAF, we included questions to explore GPs' risk assessment, estimates of stroke risk and GPs' perceptions of the risks and benefits of anticoagulation with warfarin. In addition, we explored GPs' perceived barriers to the wider uptake of anticoagulation, quality control of anticoagulation and their assessment of strategies to assist in managing NVAF.</p> <p>Results</p> <p>596 out of 924 eligible GPs responded (64.4% response rate). The majority of GPs recognised that the benefits of warfarin outweighed the risks for three case scenarios in which warfarin is recommended according to Australian guidelines. In response to a hypothetical case scenario describing a patient with a supratherapeutic INR level of 5, 41.4% of the 596 GPs (n = 247) and 22.0% (n = 131) would be "highly likely" or "likely", respectively, to cease warfarin therapy and resume at a lower dose when INR levels are within therapeutic range. Only 27.9% (n = 166/596) would reassess the patient's INR levels within one day of recording the supratherapeutic INR. Patient contraindications to warfarin was reported to "usually" or "always" apply to the patients of 40.6% (n = 242/596) of GPs when considering whether or not to prescribe warfarin. Patient refusal to take warfarin "usually" or "always" applied to the patients of 22.3% (n = 133/596) of GPs. When asked to indicate the usefulness of strategies to assist in managing NVAF, the majority of GPs (89.1%, n = 531/596) reported that they would find patient educational resources outlining the benefits and risks of available treatments "quite useful" or "very useful". Just under two-thirds (65.2%; n = 389/596) reported that they would find point of care INR testing "quite" or "very" useful. An outreach specialist service and training to enable GPs to practice stroke medicine as a special interest were also considered to be "quite" or "very useful" by 61.9% (n = 369/596) GPs.</p> <p>Conclusion</p> <p>This survey identified gaps, based on GP self-report, in the current care of NVAF. GPs themselves have provided guidance on the selection of implementation strategies to bridge these gaps. These results may inform future initiatives designed to reduce the risk of fatal and disabling stroke in NVAF.</p

Comparative proteome and peptidome analysis of the cephalic fluid secreted by Arapaima gigas (Teleostei: Osteoglossidae) during and outside parental care

Parental investment in Arapaima gigas includes nest building and guarding, followed by a care provision when a cephalic fluid is released from the parents&rsquo; head to the offspring. This fluid has presumably important functions for the offspring but so far its composition has not been characterised. In this study the proteome and peptidome of the cephalic secretion was studied in parental and non-parental fish using capillary electrophoresis coupled to mass spectrometry (CE-MS) and GeLC-MS/MS analyses. Multiple comparisons revealed 28 peptides were significantly different between males and parental males (PC-males), 126 between females and parental females (PC-females), 51 between males and females and 9 between PC-males and PC-females. Identification revealed peptides were produced in the inner ear (pcdh15b), eyes (tetraspanin and ppp2r3a), central nervous system (otud4, ribeye a, tjp1b and syn1) among others. A total of 422 proteins were also identified and gene ontology analysis revealed 28 secreted extracellular proteins. From these, 2 hormones (prolactin and stanniocalcin) and 12 proteins associated to immunological processes (serotransferrin, &alpha;-1-antitrypsin homolog, apolipoprotein A-I, and others) were identified. This study provides novel biochemical data on the lateral line fluid which will enable future hypotheses-driven experiments to better understand the physiological roles of the lateral line in chemical communication

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

Vibration sensitivity found in Caenorhabditis elegans

Mechanical sensing is important for all organisms, but is the least understood of the senses. As mechanical stimuli come in diverse forms, organisms often have sensors or sensory systems that specialise in a form of mechanical stimuli, such as touch or vibration. Here we tested the hypothesis that the nematode worm Caenorhabditis elegans exhibits a behavioural response to vibration that is distinct from its responses to touch. We show that wild type strain worms respond to sustained low frequency vibration in a manner distinct from the known responses to non-localised mechanical stimuli. Furthermore, the behavioural responses of mutant strains suggest different roles for ciliated versus non-ciliated neurons in mediating the response. Although further study is required to identify the vibration sensing pathway, our data support that C. elegans can sense substrate-borne vibrations using cells distinct from those used in gentle touch

Fish navigation in the vertical dimension: can fish use hydrostatic pressure to determine depth?

Fish live in complex volumetric habitats, and as such, face a challenging environment through which to navigate. This problem might be simplified if fish could monitor their depth and determine their position within the water column. One possible cue that they could use to ascertain their vertical position is hydrostatic pressure, which varies linearly with depth. Until recently it was assumed that fish were incapable of using hydrostatic pressure to measure depth as they do not possess a mechanism to sense absolute pressure. However, in a recent article by G. Taylor et al., we describe a novel mechanism whereby fish could determine their depth by using the rate in change of pressure mediated by changes in swim-bladder volume, together with their vertical speed. This mechanism requires fish to be able to sense changes in pressure using their swim-bladder. Here, we examine fish sensitivity towards hydrostatic pressure by reviewing the literature from behavioural and physiological experiments. This research suggests that fish are acutely sensitive to the magnitude and sign of hydrostatic pressure changes, via changes in the volume of the swim-bladder. We argue that fish have the necessary physiological measurements to sense the rate in change of pressure, meaning they are able to use the mechanism proposed by Taylor et al. to determine their vertical location. This has profound implications for the study of navigation through volumes, by providing a reliable global cue that fish can use to determine their depth. © 2010 Blackwell Publishing Ltd

Three-dimensional spatial cognition: freely swimming fish accurately learn and remember metric information in a volume

All animals live and move through three-dimensional environments, yet we do not understand how three-dimensional space is learned, remembered and used. Pelagic fish are ideal model organisms for studying three-dimensional spatial cognition as they move freely through volumes with six degrees of freedom. This is in contrast to surface-bound animals, such as rats, which are constrained to three degrees of freedom of movement. The type of movement that vertebrates display, whether freely moving through volumes (flying or swimming) or surface-bound, might shape their representation of space. We investigated true three-dimensional spatial cognition in an animal that moves freely within volumetric space. We interrogated the three-dimensional trajectories of freely swimming fish (banded tetras, Astyanax fasciatus) that were previously trained to navigate towards a reward inside a maze with horizontal and vertical components. The fish accurately encoded the rewarded three-dimensional direction. As predicted, free-swimming deviations from their original constrained trajectory were similar in both the horizontal and vertical axes, unlike in surface-bound rats. This equality between dimensions is the first direct evidence consistent with the hypothesis that the way animals move through their environment shapes how they learn and use spatial information, indicating a previously unknown adaptation in cognitive representations of space. © 2013 The Association for the Study of Animal Behaviour

Three-dimensional spatial cognition: information in the vertical dimension overrides information from the horizontal.

Fish live in three-dimensional environments, through which they swim with three translational and three rotational degrees of freedom. Navigating through such environments is recognised as a difficult problem, yet fish, and other animals that swim and fly, achieve this regularly. Despite this, the vast majority of research has considered how animals navigate horizontally from place to place and has ignored the vertical component. Here, we test the importance of the vertical axis of space for fish solving a three-dimensional spatial cognition task. We trained banded tetras (Astyanax fasciatus) to learn the route towards a goal in a rotating Y-maze in which the arms led either up and left or down and right in an environment that allowed access to visual landmarks providing horizontal and vertical information. Our results revealed that the landmarks increased navigational efficiency during training. However, these landmarks were ignored when the horizontal and vertical components were placed in conflict with each other by rotating the maze 90° during testing. From this surprising result, we conclude that the cues that are present in the vertical axis (presumably hydrostatic pressure) override landmark cues that have been shown to be salient in experiments that only consider the horizontal component of space