for Journals by Title or ISSN
for Articles by Keywords
Followed Journals
Journal you Follow: 0
Sign Up to follow journals, search in your chosen journals and, optionally, receive Email Alerts when new issues of your Followed Jurnals are published.
Already have an account? Sign In to see the journals you follow.
   [5 followers]  Follow    
  This is an Open Access Journal Open Access journal
     ISSN (Online) 2046-1402
     Published by Faculty of 1000 Homepage  [1 journal]
  • The need for antibiotic stewardship and treatment standardization in the
           care of cirrhotic patients with spontaneous bacterial peritonitis –
           a retrospective cohort study examining the effect of ceftriaxone dosing
           [v2; indexed,]

    • Authors: Laura Mazer, Elliot B. Tapper, Gail Piatkowski, Michelle Lai
      Abstract: Background: Spontaneous bacterial peritonitis (SBP) is a common, often fatal affliction for cirrhotic patients. Despite all clinical trials of ceftriaxone for SBP using 2g daily, it is often given at 1g daily. Aim: We evaluated survival after SBP as a function of ceftriaxone dosage. Methods:  A retrospective cohort of all patients who received ceftriaxone for SBP (greater than 250 neutrophils in the ascites). Results: As opposed to 1 gram, median survival is longer for patients receiving 2 grams (228 days vs. 102 days (p = 0.26) and one year survival is significantly higher (p = 0.0034).  After adjusting for baseline Model for End Stage Liver Disease (MELD) score, however, this difference was no longer significant.  Similarly, there was a significantly shorter length of intensive care for patients receiving 2 g (0.59 ± 1.78 days vs. 3.26 ± 6.9, p = 0.034), odds ratio 0.11 (95% CI 0.02 - 0.65). This difference, too, was no longer significant after controlling for the MELD score - odds ratio 0.21 (95% CI 0.04 - 1.07). Additionally, 70% of patients received at least one additional antibiotic; over 25 different medications were used in various combinations. Conclusions:  Patients receiving 2 g of ceftriaxone may require fewer intensive care days and may enjoy an improved survival compared to those receiving 1 g daily. The complexity of antibiotic regimens to which cirrhotic patients are exposed must be studied further and rationalized.  We recommend fastidious antibiotic stewardship for patients with cirrhosis. Efforts should be made to craft local standards for the treatment of SBP that include appropriate antibiotic selection and dose.
      PubDate: 2014-07-14
      DOI: 10.12688/f1000research.3-57.v2
      Issue No: Vol. 3 (2014)
  • Porting and using PanGIA for Cytoscape 3: challenges and solutions [v1;

    • Authors: David Welker, Barry Demchak
      Abstract: Much of the biologically significant functionality in Cytoscape is contained within third-party add-ons, called plugins in Cytoscape 2 and apps in Cytoscape 3. In the transition from Cytoscape 2 to Cystoscape 3, some of the underlying assumptions upon which plugins relied changed, requiring a significant porting effort for plugins to work as Cytoscape 3 apps. PanGIA is a Cytoscape add-on ( designed to analyze and visualize genetic interaction data in light of physical interaction data. In order to convert the PanGIA plugin to an app, various challenges, including those related to a transformed data model, concurrency, and randomization had to be overcome. In the process, the ability to control randomization was added to the GUI, a feature which was not only integral to the porting process, but which also ensures more easily reproducible scientific analysis for PanGIA users. Most authors of Cytoscape 2 plugins will face similar challenges porting their software to work with Cytoscape 3, and this paper gives details of how the PanGIA port addressed them.
      PubDate: 2014-07-01
      DOI: 10.12688/f1000research.4546.1
      Issue No: Vol. 3 (2014)
  • setsApp: Set operations for Cytoscape Nodes and Edges [v1; indexed,

    • Authors: John H. Morris, Allan Wu, Nadezhda T. Doncheva, Mario Albrecht, Thomas E Ferrin
      Abstract: setsApp ( is a relatively simple Cytoscape 3 app for users to handle groups of nodes and/or edges. It supports several important biological workflows and enables various set operations. setsApp provides basic tools to create sets of nodes or edges, import or export sets, and perform standard set operations (union, difference, intersection) on those sets. The sets functionality is also exposed to users and app developers in the form of a set of commands that can be used for scripting purposes or integrated in other Cytoscape apps.
      PubDate: 2014-07-01
      DOI: 10.12688/f1000research.4392.1
      Issue No: Vol. 3 (2014)
  • Enrichment Map – a Cytoscape app to visualize and explore OMICs
           pathway enrichment results [v1; indexed,]

    • Authors: Ruth Isserlin, Daniele Merico, Veronique Voisin, Gary D. Bader
      Abstract: High-throughput OMICs experiments generate signals for millions of entities (i.e. genes, proteins, metabolites or any measurable biological entity) in the cell. In an effort to summarize and explore these signals, expression results are examined in the context of known pathways and processes, through enrichment analysis to generate a set of pathways and processes that is significantly enriched. Due to the high redundancy in annotation resources this often results in hundreds of sets. To facilitate the analysis of these results, we have developed the Enrichment Map app to visualize enrichments as a network. We have updated Enrichment Map to support Cytoscape 3, and have added additional features including new data formats and command line access.
      PubDate: 2014-07-01
      DOI: 10.12688/f1000research.4536.1
      Issue No: Vol. 3 (2014)
  • BridgeDb app: unifying identifier mapping services for Cytoscape [v1;

    • Authors: Jianjiong Gao, Chao Zhang, Martijn van Iersel, Li Zhang, Dong Xu, Nikolaus Schultz, Alexander R. Pico
      Abstract: The BridgeDb app for Cytoscape allows users to map and annotate identifiers of genes, proteins and metabolites in the context of biological networks. The app greatly simplifies the identifier mapping process in Cytoscape by providing a unified interface to different mapping resources and services. The app also provides a programming interface via Cytoscape Commands that can be utilized for identifier mapping by other Cytoscape apps. In this article we provide a technical guide to the BridgeDb app for mapping identifiers in Cytoscape.
      PubDate: 2014-07-01
      DOI: 10.12688/f1000research.4521.1
      Issue No: Vol. 3 (2014)
  • Ecological implications of reduced pollen deposition in alpine plants: a
           case study using a dominant cushion plant species [v1; indexed,

    • Authors: Anya Reid, Robyn Hooper, Olivia Molenda, Christopher J. Lortie
      Abstract: The reproductive assurance hypothesis states that self-incompatible female plants must produce twice the number of seeds relative to their self-compatible hermaphroditic counterparts to persist in gynodioecious populations. This is a viable life-history strategy, provided that pollination rates are sufficiently high. However, reduced pollination rates in alpine plants are likely due to climate induced plant-pollinator mismatches and general declines in pollinators. Using a gynodioecious population of the dominant plant Silene acaulis (Caryophyllaceae), we tested the reproductive assurance hypothesis and also the stress gradient hypothesis with a series of pollinator exclusion trials and extensive measurements of subsequent reproductive output (gender ratio, plant size, percent fruit-set, fruit weight, seeds per fruit, total seeds, seed weight, and seed germination). The reproductive assurance hypothesis was supported with female plants being more sensitive to and less likely to be viable under reductions in pollination rates. These findings are the first to show that the stress gradient hypothesis is also supported under a gradient of pollen supply instead of environmental limitations. Beneficiary abundance was negatively correlated to percent fruit-set under current pollen supply, but became positive under reduced pollen supply suggesting that there are important plant-plant-pollinator interactions related to reproduction in these alpine plant species.
      PubDate: 2014-06-19
      DOI: 10.12688/f1000research.4382.1
      Issue No: Vol. 3 (2014)
  • Ten things to get right for marine conservation planning in the Coral
           Triangle [v2; indexed,]

    • Authors: Rebecca Weeks, Robert L. Pressey, Joanne R. Wilson, Maurice Knight, Vera Horigue, Rene A. Abesamis, Renerio Acosta, Jamaluddin Jompa
      Abstract: Systematic conservation planning increasingly underpins the conservation and management of marine and coastal ecosystems worldwide. Amongst other benefits, conservation planning provides transparency in decision-making, efficiency in the use of limited resources, the ability to minimise conflict between diverse objectives, and to guide strategic expansion of local actions to maximise their cumulative impact. The Coral Triangle has long been recognised as a global marine conservation priority, and has been the subject of huge investment in conservation during the last five years through the Coral Triangle Initiative on Coral Reefs, Fisheries and Food Security. Yet conservation planning has had relatively little influence in this region. To explore why this is the case, we identify and discuss 10 challenges that must be resolved if conservation planning is to effectively inform management actions in the Coral Triangle. These are: making conservation planning accessible; integrating with other planning processes; building local capacity for conservation planning; institutionalising conservation planning within governments; integrating plans across governance levels; planning across governance boundaries; planning for multiple tools and objectives; understanding limitations of data; developing better measures of progress and effectiveness; and making a long term commitment. Most important is a conceptual shift from conservation planning undertaken as a project, to planning undertaken as a process, with dedicated financial and human resources committed to long-term engagement.
      PubDate: 2014-06-11
      DOI: 10.12688/f1000research.3886.2
      Issue No: Vol. 3 (2014)
  • Mutation extraction tools can be combined for robust recognition of
           genetic variants in the literature [v2; indexed,]

    • Authors: Antonio Jimeno Yepes, Karin Verspoor
      Abstract: As the cost of genomic sequencing continues to fall, the amount of data being collected and studied for the purpose of understanding the genetic basis of disease is increasing dramatically. Much of the source information relevant to such efforts is available only from unstructured sources such as the scientific literature, and significant resources are expended in manually curating and structuring the information in the literature. As such, there have been a number of systems developed to target automatic extraction of mutations and other genetic variation from the literature using text mining tools. We have performed a broad survey of the existing publicly available tools for extraction of genetic variants from the scientific literature. We consider not just one tool but a number of different tools, individually and in combination, and apply the tools in two scenarios. First, they are compared in an intrinsic evaluation context, where the tools are tested for their ability to identify specific mentions of genetic variants in a corpus of manually annotated papers, the Variome corpus. Second, they are compared in an extrinsic evaluation context based on our previous study of text mining support for curation of the COSMIC and InSiGHT databases. Our results demonstrate that no single tool covers the full range of genetic variants mentioned in the literature. Rather, several tools have complementary coverage and can be used together effectively. In the intrinsic evaluation on the Variome corpus, the combined performance is above 0.95 in F-measure, while in the extrinsic evaluation the combined recall performance is above 0.71 for COSMIC and above 0.62 for InSiGHT, a substantial improvement over the performance of any individual tool. Based on the analysis of these results, we suggest several directions for the improvement of text mining tools for genetic variant extraction from the literature.
      PubDate: 2014-06-10
      DOI: 10.12688/f1000research.3-18.v2
      Issue No: Vol. 3 (2014)
  • Epiphyte response to drought and experimental warming in an Andean cloud
           forest [v2; indexed,]

    • Authors: Joshua M. Rapp, Miles R. Silman
      Abstract: The high diversity and abundance of vascular epiphytes in tropical montane cloud forest is associated with frequent cloud immersion, which is thought to protect plants from drought stress. Increasing temperature and rising cloud bases associated with climate change may increase epiphyte drought stress, leading to species and biomass loss. We tested the hypothesis that warmer and drier conditions associated with a lifting cloud base will lead to increased mortality and/or decreased recruitment of epiphyte ramets, altering species composition in epiphyte mats. By using a reciprocal transplant design, where epiphyte mats were transplanted across an altitudinal gradient of increasing cloud immersion, we differentiated between the effects of warmer and drier conditions from the more general prediction of niche theory that transplanting epiphytes in any direction away from their home elevation should result in reduced performance. Effects differed among species, but effects were generally stronger and more negative for epiphytes in mats transplanted down slope from the highest elevation, into warmer and drier conditions, than for epiphyte mats transplanted from other elevations. In contrast, epiphytes from lower elevations showed greater resistance to drought in all treatments. Epiphyte community composition changed with elevation, but over the timescale of the experiment there were no consistent changes in species composition. Our results suggest some epiphytes may show resistance to climate change depending on the environmental and evolutionary context. In particular, sites where high rainfall makes cloud immersion less important for epiphyte water-balance, or where occasional drought has previously selected for drought-resistant taxa, may be less adversely affected by predicted climate changes.
      PubDate: 2014-06-06
      DOI: 10.12688/f1000research.3-7.v2
      Issue No: Vol. 3 (2014)
  • Lung transplantation in an intensive care patient with pulmonary alveolar
           microlithiasis - a case report [v1; indexed,]

    • Authors: Bülent Güçyetmez, Aylin Ogan, Aylin Çimet Ayyıldız, Berrin Yalçın Güder, Walter Klepetko
      Abstract: Introduction: Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease characterized by the deposition of phosphate and calcium in the alveoli. The disease progresses asymptomatically until later stages. When it becomes symptomatic, lung transplantations performed before the onset of right heart failure may improve life expectancy and quality. Here we present a case report concerning the very first Turkish PAM patient to have undergone lung transplantation surgery. Patient information: A 52 year-old female, Caucasian patient, already diagnosed with PAM in infancy, was admitted to the intensive care unit, diagnosed with pneumonia and hospitalized for 20 days. We decided to refer the patient to a specialized center for lung transplantation. Bilateral lung transplantation was performed in Vienna 14 months later and no recurrence was observed during the first postoperative year. Conclusion: Bilateral lung transplantation may improve both the life expectancy and the quality of life of PAM diagnosed patients with severe respiratory failure who do not suffer from right heart failure. The risk of recurrence should not be considered as a justifying reason to avoid transplantation as a treatment method.
      PubDate: 2014-05-28
      DOI: 10.12688/f1000research.4035.1
      Issue No: Vol. 3 (2014)
  • Recent trends in airway management: we are not ready to give up fiberoptic
           endoscopy [v1; indexed,]

    • Authors: Davide Cattano, Rabail Chaudhry, Rashida Callender, Peter Killoran, Carin Hagberg
      Abstract: The purpose of this correspondence is to discuss recent findings related to current trends in airway management and to discuss the utilization rates of video laryngoscopes versus traditional techniques in USA, UK, and Canada. To highlight the increased use of video laryngoscopes in difficult airway situations, data on the use of alternative airway devices at our institution collected from 2008 to 2010 are presented alongside the results of previously published surveys collected from 2002 to 2013.
      PubDate: 2014-05-16
      DOI: 10.12688/f1000research.3829.1
      Issue No: Vol. 3 (2014)
  • Colonoscopic polyp detection rate is stable throughout the workday
           including evening colonoscopy sessions [v1; indexed,]

    • Authors: David Thurtle, Michael Pullinger, Jordan Tsigarides, Iris McIntosh, Carla Steytler, Ian Beales
      Abstract: Objective: Polyp detection rate (PDR) is an accepted measure of colonoscopy quality. Several factors may influence PDR including time of procedure and order of colonoscopy within a session. Our unit provides evening colonoscopy lists (6-9 pm). We examined whether colonoscopy performance declines in the evening. Design: Data for all National Health Service (NHS) outpatient colonoscopies performed at Norfolk and Norwich University Hospital in 2011 were examined. Timing, demographics, indication and colonoscopy findings were recorded. Statistical analysis was performed using multivariate regression. Results: Data from 2576 colonoscopies were included: 1163 (45.1%) in the morning, 1123 (43.6%) in the afternoon and 290 (11.3%) in the evening.  Overall PDR was 40.80%. Males, increasing age and successful caecal intubation were all significantly associated with higher polyp detection. The indications ‘faecal occult blood screening’ (p
      PubDate: 2014-05-13
      DOI: 10.12688/f1000research.4045.1
      Issue No: Vol. 3 (2014)
  • Exercise-induced arterial hypertension - an independent factor for
           hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation
           in athletes? [v1; indexed,]

    • Authors: Roman Leischik, Norman Spelsberg, Hiltrud Niggemann, Birgit Dworrak, Klaus Tiroch
      Abstract: Background: Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the “cardiac fatigue” caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. Methods: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. Results: When comparing triathletes with LVM 220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Conclusion: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.
      PubDate: 2014-05-12
      DOI: 10.12688/f1000research.4001.1
      Issue No: Vol. 3 (2014)
  • An analysis on the entity annotations in biological corpora [v1; indexed,

    • Authors: Mariana Neves
      Abstract: Collection of documents annotated with semantic entities and relationships are crucial resources to support development and evaluation of text mining solutions for the biomedical domain. Here I present an overview of 36 corpora and show an analysis on the semantic annotations they contain. Annotations for entity types were classified into six semantic groups and an overview on the semantic entities which can be found in each corpus is shown. Results show that while some semantic entities, such as genes, proteins and chemicals are consistently annotated in many collections, corpora available for diseases, variations and mutations are still few, in spite of their importance in the biological domain.
      PubDate: 2014-04-25
      DOI: 10.12688/f1000research.3216.1
      Issue No: Vol. 3 (2014)
  • Early elevated serum gamma glutamyl transpeptidase after liver
           transplantation is associated with better survival [v1; indexed,

    • Authors: Edris M Alkozai, Ton Lisman, Robert J Porte, Maarten W Nijsten
      Abstract: Background: Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that plays a key role in the synthesis of the antioxidant glutathione. Epidemiological studies have linked high GGT with an increased risk of morbidity and cardiovascular mortality. In contrast, GGT is usually elevated in liver transplant recipients that experience good outcomes. Aims: To study if and how GGT is correlated with mortality following liver transplantation. Methods: We analyzed the prognostic relevance of serum GGT levels during the early and late postoperative period after liver transplantation in 522 consecutive adults. We also studied alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Results: Early after transplantation, the peak median (interquartile range) GGT levels were significantly higher in patients who survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84-239) U/l, p
      PubDate: 2014-04-03
      DOI: 10.12688/f1000research.3316.1
      Issue No: Vol. 3 (2014)
  • Resolving the paradox for protein aggregation diseases: NMR structure and
           dynamics of the membrane-embedded P56S-MSP causing ALS imply a common
           mechanism for aggregation-prone proteins to attack membranes [v2; indexed,

    • Authors: Haina Qin, Liangzhong Lim, Yuanyuan Wei, Garvita Gupta, Jianxing Song
      Abstract: Paradoxically, aggregation of specific proteins is characteristic of many human diseases and aging, yet aggregates have increasingly been found to be unnecessary for initiating pathogenesis. Here we determined the NMR topology and dynamics of a helical mutant in a membrane environment transformed from the 125-residue cytosolic all-β MSP domain of vesicle-associated membrane protein-associated protein B (VAPB) by the ALS-causing P56S mutation. Despite its low hydrophobicity, the P56S major sperm protein (MSP) domain becomes largely embedded in the membrane environment with high backbone rigidity. Furthermore it is composed of five helices with amphiphilicity comparable to those of the partly-soluble membrane toxin mellitin and α-synuclein causing Parkinson's disease. Consequently, the mechanism underlying this chameleon transformation becomes clear: by disrupting the specific tertiary interaction network stabilizing the native all-β MSP fold to release previously-locked amphiphilic segments, the P56S mutation acts to convert the classic MSP fold into a membrane-active protein that is fundamentally indistinguishable from mellitin and α-synuclein which are disordered in aqueous solution but spontaneously partition into membrane interfaces driven by hydrogen-bond energetics gained from forming α-helix in the membrane environments. As segments with high amphiphilicity exist in all proteins, our study successfully resolves the paradox by deciphering that the proteins with a higher tendency to aggregate have a stronger potential to partition into membranes through the same mechanism as α-synuclein to initially attack membranes to trigger pathogenesis without needing aggregates. This might represent the common first step for various kinds of aggregated proteins to trigger familiar, sporadic and aging diseases. Therefore the homeostasis of aggregated proteins in vivo is the central factor responsible for a variety of human diseases including aging. The number and degree of the membrane attacks by aggregated proteins may act as an endogenous clock to count down the aging process. Consequently, a key approach to fight against them is to develop strategies and agents to maintain or even enhance the functions of the degradation machineries.
      PubDate: 2014-07-22
      DOI: 10.12688/f1000research.2-221.v2
      Issue No: Vol. 2 (2014)
  • C-Sibelia: an easy-to-use and highly accurate tool for bacterial genome
           comparison [v1; indexed,]

    • Authors: Ilya Minkin, Hoa Pham, Ekaterina Starostina, Nikolay Vyahhi, Son Pham
      Abstract: We present C-Sibelia, a highly accurate and easy-to-use software tool for comparing two closely related bacterial genomes, which can be presented as either finished sequences or fragmented assemblies. C-Sibelia takes as input two FASTA files and produces: (1) a VCF file containing all identified single nucleotide variations and indels; (2) an XMFA file containing alignment information. The software also produces Circos diagrams visualizing high level genomic architecture for rearrangement analyses. C-Sibelia is a part of the Sibelia comparative genomics suite, which is freely available under the GNU GPL v.2 license at C-Sibelia is compatible with Unix-like operating systems. A web-based version of the software is available at
      PubDate: 2013-11-25
      DOI: 10.12688/f1000research.2-258.v1
      Issue No: Vol. 2 (2013)
  • The electrostatic profile of consecutive Cβ atoms applied to protein
           structure quality assessment [v2; indexed,]

    • Authors: Sandeep Chakraborty, Ravindra Venkatramani, Basuthkar J. Rao, Bjarni Asgeirsson, Abhaya M. Dandekar
      Abstract: The structure of a protein provides insight into its physiological interactions with other components of the cellular soup. Methods that predict putative structures from sequences typically yield multiple, closely-ranked possibilities. A critical component in the process is the model quality assessing program (MQAP), which selects the best candidate from this pool of structures. Here, we present a novel MQAP based on the physical properties of sidechain atoms. We propose a method for assessing the quality of protein structures based on the electrostatic potential difference (EPD) of Cβ atoms in consecutive residues. We demonstrate that the EPDs of Cβ atoms on consecutive residues provide unique signatures of the amino acid types. The EPD of Cβ atoms are learnt from a set of 1000 non-homologous protein structures with a resolution cuto of 1.6 Å obtained from the PISCES database. Based on the Boltzmann hypothesis that lower energy conformations are proportionately sampled more, and on Annsen's thermodynamic hypothesis that the native structure of a protein is the minimum free energy state, we hypothesize that the deviation of observed EPD values from the mean values obtained in the learning phase is minimized in the native structure. We achieved an average specificity of 0.91, 0.94 and 0.93 on hg_structal, 4state_reduced and ig_structal decoy sets, respectively, taken from the Decoys `R' Us database. The source code and manual is made available at and permanently available on 10.5281/zenodo.7134.
      PubDate: 2013-11-15
      DOI: 10.12688/f1000research.2-243.v2
      Issue No: Vol. 2 (2013)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2014