Showing papers by "Ghent University published in 2012"
TL;DR: In this paper, results from searches for the standard model Higgs boson in proton-proton collisions at 7 and 8 TeV in the CMS experiment at the LHC, using data samples corresponding to integrated luminosities of up to 5.8 standard deviations.
8,857 citations
Katholieke Universiteit Leuven1, Ghent University2, Karolinska Institutet3, Cairo University4, University of São Paulo5, Cincinnati Children's Hospital Medical Center6, Innsbruck Medical University7, University of Duisburg-Essen8, Tufts University9, University of Aberdeen10, University of California, San Diego11, University College Dublin12, University of the Witwatersrand13, Brown University14, Heidelberg University15, Jikei University School of Medicine16
4,482 citations
Daniel J. Klionsky1, Fábio Camargo Abdalla2, Hagai Abeliovich3, Robert T. Abraham4 +1284 more•Institutions (463)
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
4,316 citations
Wellcome Trust Sanger Institute1, Broad Institute2, University of Groningen3, University of Pittsburgh4, Cedars-Sinai Medical Center5, Yale University6, University of Cambridge7, University of Chicago8, Harvard University9, Katholieke Universiteit Leuven10, University of Liège11, King's College London12, Université de Montréal13, New Jersey Institute of Technology14, Cleveland Clinic15, Peninsula College of Medicine and Dentistry16, Université libre de Bruxelles17, Aarhus University18, University of Adelaide19, University of Kiel20, Flinders University21, McGill University22, Ludwig Maximilian University of Munich23, Charité24, Icahn School of Medicine at Mount Sinai25, University of Bonn26, Karolinska Institutet27, Torbay Hospital28, University of Auckland29, Christchurch Hospital30, Imperial College London31, Queen's University32, University of Oslo33, Lithuanian University of Health Sciences34, Emory University35, Casa Sollievo della Sofferenza36, Ghent University37, University of Western Australia38, University of Edinburgh39, Queensland Health40, Newcastle University41, University of Dundee42, University of Manchester43, University of Amsterdam44, University of Maribor45, Royal Hospital for Sick Children46, Guy's and St Thomas' NHS Foundation Trust47, QIMR Berghofer Medical Research Institute48, Norfolk and Norwich University Hospital49, Leiden University50, Technische Universität München51, University of Toronto52, University of Pennsylvania53, Johns Hopkins University54, University of Queensland55
TL;DR: A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
Abstract: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
4,094 citations
TL;DR: A high-quality genome sequence of domesticated tomato is presented, a draft sequence of its closest wild relative, Solanum pimpinellifolium, is compared, and the two tomato genomes are compared to each other and to the potato genome.
Abstract: Tomato (Solanum lycopersicum) is a major crop plant and a model system for fruit development. Solanum is one of the largest angiosperm genera1 and includes annual and perennial plants from diverse habitats. Here we present a high-quality genome sequence of domesticated tomato, a draft sequence of its closest wild relative, Solanum pimpinellifolium2, and compare them to each other and to the potato genome (Solanum tuberosum). The two tomato genomes show only 0.6% nucleotide divergence and signs of recent admixture, but show more than 8% divergence from potato, with nine large and several smaller inversions. In contrast to Arabidopsis, but similar to soybean, tomato and potato small RNAs map predominantly to gene-rich chromosomal regions, including gene promoters. The Solanum lineage has experienced two consecutive genome triplications: one that is ancient and shared with rosids, and a more recent one. These triplications set the stage for the neofunctionalization of genes controlling fruit characteristics, such as colour and fleshiness.
2,687 citations
French Institute of Health and Medical Research1, University of Paris-Sud2, Institut Gustave Roussy3, University of Texas Southwestern Medical Center4, Thomas Jefferson University5, University of Massachusetts Medical School6, Roswell Park Cancer Institute7, Johns Hopkins University School of Medicine8, Penn State Milton S. Hershey Medical Center9, Goethe University Frankfurt10, St. Jude Children's Research Hospital11, University of Zurich12, University College London13, South Australia Pathology14, University of Adelaide15, Ludwig Institute for Cancer Research16, University of Graz17, Istituto Superiore di Sanità18, University of Michigan19, Northwestern University20, University of Rome Tor Vergata21, University of Cambridge22, University of Bern23, Ghent University24, Harvard University25, Karolinska Institutet26, University of Leicester27
TL;DR: A functional classification of cell death subroutines is proposed that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic programmed cell death, regulated necrosis, autophagic cell death and mitotic catastrophe.
Abstract: In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.
2,238 citations
TL;DR: An overview of the current state-of-the-art in silicon nanophotonic ring resonators is presented in this paper, where the basic theory of ring resonance is discussed and applied to the peculiarities of submicron silicon photonic wire waveguides: the small dimensions and tight bend radii, sensitivity to perturbations and the boundary conditions of the fabrication processes.
Abstract: An overview is presented of the current state-of-the-art in silicon nanophotonic ring resonators. Basic theory of ring resonators is discussed, and applied to the peculiarities of submicron silicon photonic wire waveguides: the small dimensions and tight bend radii, sensitivity to perturbations and the boundary conditions of the fabrication processes. Theory is compared to quantitative measurements. Finally, several of the more promising applications of silicon ring resonators are discussed: filters and optical delay lines, label-free biosensors, and active rings for efficient modulators and even light sources.
1,989 citations
TL;DR: The role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and the effect of therapy-resistant cancer microevolution on ICD are discussed.
Abstract: Although it was thought that apoptotic cells, when rapidly phagocytosed, underwent a silent death that did not trigger an immune response, in recent years a new concept of immunogenic cell death (ICD) has emerged. The immunogenic characteristics of ICD are mainly mediated by damage-associated molecular patterns (DAMPs), which include surface-exposed calreticulin (CRT), secreted ATP and released high mobility group protein B1 (HMGB1). Most DAMPs can be recognized by pattern recognition receptors (PRRs). In this Review, we discuss the role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and the effect of therapy-resistant cancer microevolution on ICD.
1,736 citations
University of Amsterdam1, Ghent University2, University of Chicago3, University of Pennsylvania4, Auckland City Hospital5, University of Antwerp6, University of New South Wales7, Katholieke Universiteit Leuven8, St Thomas' Hospital9, University of Nottingham10, University of Zagreb11, Northwestern University12, Medical University of Łódź13, University of Aberdeen14, Innsbruck Medical University15, Medical University of South Carolina16, University of Southampton17, Children's Hospital of Philadelphia18, University of São Paulo19, National University of Singapore20, University of Adelaide21, Flinders University22
TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 as discussed by the authors is the update of similar evidence-based position papers published in 2005 and 2007, it contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinositis, control of disease, and better definitions for rhinosinitis in children.
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.
1,608 citations
TL;DR: This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate.
Abstract: Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.
1,471 citations
University of Cologne1, Max Planck Society2, University of Bonn3, Ghent University4, Broad Institute5, Stanford University6, Technical University of Dortmund7, Columbia University8, University of Melbourne9, St. Vincent's Health System10, University of Jena11, Casa Sollievo della Sofferenza12, University of Groningen13, VU University Amsterdam14, University of Bologna15, University of Liverpool16, University of Oslo17, University of Zurich18, Peter MacCallum Cancer Centre19, Institut Gustave Roussy20, University of Grenoble21, Vanderbilt University22, Harvard University23, University of Washington24, University of Strasbourg25
TL;DR: This study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.
Abstract: Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice(4). Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.
La Trobe University1, Harvard University2, German Cancer Research Center3, Yale University4, Morehouse School of Medicine5, Autonomous University of Barcelona6, University of Massachusetts Medical School7, Semmelweis University8, Cardiff University9, Ikerbasque10, Karolinska Institutet11, Pohang University of Science and Technology12, Allahabad University13, Ghent University14, University of Melbourne15, London Metropolitan University16, Erasmus University Rotterdam17, University of Mainz18, National University of Singapore19, University of Oslo20, University of Gothenburg21, University of Valencia22, Umeå University23, University of Freiburg24, University of Amsterdam25, Utrecht University26, Johns Hopkins University27, Mayo Clinic28, Ohio State University29, University of Cambridge30, University of Zurich31, Curie Institute32, Michigan State University33, Autonomous University of Madrid34, University of Helsinki35, Aalborg University36, University of Louisville37, Carlos III Health Institute38, Centre national de la recherche scientifique39, Heidelberg University40
TL;DR: Vesiclepedia is a community-annotated compendium of molecular data on extracellular vesicles that aims to provide a single authoritative source for information on vesicle structure and function.
Abstract: Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
Eindhoven University of Technology1, Queensland University of Technology2, Capgemini3, University of Rome Tor Vergata4, Humboldt University of Berlin5, Software AG6, University of Padua7, Polytechnic University of Catalonia8, Hewlett-Packard9, Ghent University10, New Mexico State University11, IBM12, University of Milan13, University of Tartu14, University of Vienna15, Technical University of Lisbon16, Telecom SudParis17, Rabobank18, Infosys19, University of Calabria20, Fujitsu21, Pennsylvania State University22, University of Bari23, University of Bologna24, Vienna University of Economics and Business25, Free University of Bozen-Bolzano26, Stevens Institute of Technology27, Indian Council of Agricultural Research28, Pontifical Catholic University of Chile29, University of Haifa30, Ulsan National Institute of Science and Technology31, Cranfield University32, Katholieke Universiteit Leuven33, Deloitte34, Tsinghua University35, University of Innsbruck36, Hasso Plattner Institute37
TL;DR: This manifesto hopes to serve as a guide for software developers, scientists, consultants, business managers, and end-users to increase the maturity of process mining as a new tool to improve the design, control, and support of operational business processes.
Abstract: Process mining techniques are able to extract knowledge from event logs commonly available in today’s information systems. These techniques provide new means to discover, monitor, and improve processes in a variety of application domains. There are two main drivers for the growing interest in process mining. On the one hand, more and more events are being recorded, thus, providing detailed information about the history of processes. On the other hand, there is a need to improve and support business processes in competitive and rapidly changing environments. This manifesto is created by the IEEE Task Force on Process Mining and aims to promote the topic of process mining. Moreover, by defining a set of guiding principles and listing important challenges, this manifesto hopes to serve as a guide for software developers, scientists, consultants, business managers, and end-users. The goal is to increase the maturity of process mining as a new tool to improve the (re)design, control, and support of operational business processes.
TL;DR: Morphological and molecular identification demonstrated that the population of cyst nematodes from a wheat field in Aïn Jemâa, Morocco was H. latipons, a new record of H. avenae, and care should be taken to prevent the spread to other regions.
Abstract: From May to June 2011, during a survey of the wheat-growing areas in Meknes in the Sais Region of Morocco, several cyst nematode populations were detected. Sampling was performed 1 month before wheat (Triticum durum) harvest, in fields showing patches of stunted plants. Plants were growing poorly, had chlorotic lower leaves, and a reduced numbers of ears. Root systems were short and had a bushy appearance because of increased secondary root production. No cysts were visible on the roots, but were found in the soil. Cysts were collected from soil on 200-μm sieves by the modified Cobb decanting and sieving method (1) and identified by morphology and internal transcribed spacer (ITS)-rDNA sequencing. All isolates were identified as Heterodera avenae except the isolate from Ain Jemâa. From the latter, key morphological features from cysts and second-stage juveniles (J2) were determined. The cysts (n = 10) had the following characteristics: bifenestrate vulval cone, body length without neck 590 μm (551 to 632 μm), body width 393 μm (310 to 490 μm), neck length 75 μm (65 to 90 μm), fenestra length 64 μm (60 to 72 μm) and width 21 μm (18 to 25 μm), underbridge length 96 μm (85 to 115 μm), vulval slit length 8 μm (7 to 9 μm), vulva bridge width 27 μm (24 to 33 μm), and bullae absent. The J2s (n = 10) had the following characteristics: body length 445 μm (412 to 472 μm), body width 19 μm (19 to 21 μm), stylet length 24 μm (23 to 25 μm), four lateral lines, tail length 50 μm (46 to 54 μm), and hyaline terminal tail 28 μm (24 to 31 μm). Values of the morphological characters were within the range of H. latipons reported by Handoo (3). The bifenestrate cysts with a strong underbridge and no bullae and J2 with a tail length greater than 40 μm, a stylet longer than 15 μm, and four incisures in the lateral field were typical for H. latipons. To confirm the identification, molecular observations were made. DNA was extracted from three juveniles from three different cysts separately (4). The ITS-rDNA region was amplified using the primers 5'-CGT AAC AAG GTA GCT GTA G-3' and 5'-TCC TCC GCT AAA TGA TAT G-3' as described by Ferris et al. (2). This resulted in a 1,040-bp DNA fragment. The PCR-products were purified and sequenced (Macrogen, Inc., Seoul, Korea). All sequences obtained (GenBank Accession Nos. per cyst: JQ319035, JQ319036, and JQ319037) were compared with sequences available from the GenBank database ( www.ncbi.nlm.nih.gov ), including several species of Heterodera. This comparison revealed a sequence similarity of 97 to 99% with H. latipons and 89% or lower with any other species of Heterodera. Morphological and molecular identification demonstrated that the population of cyst nematodes from a wheat field in Ain Jemâa, Morocco was H. latipons. In the patches with poor growing plants, 65 cysts per 100 cm3 soil were found. To our knowledge, this detection represents a new record of H. latipons. Since the nematode can cause considerable damage to wheat, one of the main cereals produced in Morocco, care should be taken to prevent the spread to other regions. References: (1) K. R. Barker. Page 19 in: An Advanced Treatise on Meloidogyne. Vol II. Methodology. C. C. Carter and J. N. Sasser, eds. North Carolina State University Graphics, Raleigh, 1985. (2) V. R. Ferris et al. Fundam. Appl. Nematol. 16:177, 1993. (3) Z. A. Handoo. J. Nematol. 34:250, 2002. (4) M. Holterman et al. Mol. Biol. Evol. 23:1792, 2006.
TL;DR: An overview on the different rapid prototyping techniques suitable for the processing of hydrogel materials, and a primary distinction will be made between (i) laser-based, (ii) nozzle- based, and (iii) printer-based systems.
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TL;DR: The consequences of the presence and magnitude of different costs during different phases of the dispersal process, and their internal organisation through covariation with other life‐history traits are synthesised with respect to potential consequences for species conservation and the need for development of a new generation of spatial simulation models.
Abstract: Dispersal costs can be classified into energetic, time, risk and opportunity costs and may be levied directly or deferred during departure, transfer and settlement. They may equally be incurred during life stages before the actual dispersal event through investments in special morphologies. Because costs will eventually determine the performance of dispersing individuals and the evolution of dispersal, we here provide an extensive review on the different cost types that occur during dispersal in a wide array of organisms, ranging from micro-organisms to plants, invertebrates and vertebrates. In general, costs of transfer have been more widely documented in actively dispersing organisms, in contrast to a greater focus on costs during departure and settlement in plants and animals with a passive transfer phase. Costs related to the development of specific dispersal attributes appear to be much more prominent than previously accepted. Because costs induce trade-offs, they give rise to covariation between dispersal and other life-history traits at different scales of organismal organisation. The consequences of (i) the presence and magnitude of different costs during different phases of the dispersal process, and (ii) their internal organisation through covariation with other life-history traits, are synthesised with respect to potential consequences for species conservation and the need for development of a new generation of spatial simulation models.
TL;DR: This megastudy presents age-of-acquisition ratings for 30,121 English content words (nouns, verbs, and adjectives) using the Web-based crowdsourcing technology offered by the Amazon Mechanical Turk to indicate that the ratings collected are as valid and reliable as those collected in laboratory conditions.
Abstract: We present age-of-acquisition (AoA) ratings for 30,121 English content words (nouns, verbs, and adjectives). For data collection, this megastudy used the Web-based crowdsourcing technology offered by the Amazon Mechanical Turk. Our data indicate that the ratings collected in this way are as valid and reliable as those collected in laboratory conditions (the correlation between our ratings and those collected in the lab from U.S. students reached .93 for a subsample of 2,500 monosyllabic words). We also show that our AoA ratings explain a substantial percentage of the variance in the lexical-decision data of the English Lexicon Project, over and above the effects of log frequency, word length, and similarity to other words. This is true not only for the lemmas used in our rating study, but also for their inflected forms. We further discuss the relationships of AoA with other predictors of word recognition and illustrate the utility of AoA ratings for research on vocabulary growth.
Finnish Institute of Occupational Health1, University of Helsinki2, University College London3, University of Edinburgh4, Stockholm University5, RMIT University6, Karolinska Institutet7, Federal Institute for Occupational Safety and Health8, Université libre de Bruxelles9, Ghent University10, University of Düsseldorf11, University of Bristol12, French Institute of Health and Medical Research13, Mid Sweden University14, Queen's University Belfast15, Umeå University16, University of Copenhagen17, University of Turku18, Turku University Hospital19, Uppsala University20
TL;DR: The findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking.
TL;DR: The proposed risk assessment scheme for systemic compounds was shown to be applicable to assess the risk for side-effects of neonicotinoids as it considers the effect on different life stages and different levels of biological organization (organism versus colony).
Abstract: Neonicotinoid insecticides are successfully applied to control pests in a variety of agricultural crops; however, they may not only affect pest insects but also non-target organisms such as pollinators. This review summarizes, for the first time, 15 years of research on the hazards of neonicotinoids to bees including honey bees, bumble bees and solitary bees. The focus of the paper is on three different key aspects determining the risks of neonicotinoid field concentrations for bee populations: (1) the environmental neonicotinoid residue levels in plants, bees and bee products in relation to pesticide application, (2) the reported side-effects with special attention for sublethal effects, and (3) the usefulness for the evaluation of neonicotinoids of an already existing risk assessment scheme for systemic compounds. Although environmental residue levels of neonicotinoids were found to be lower than acute/chronic toxicity levels, there is still a lack of reliable data as most analyses were conducted near the detection limit and for only few crops. Many laboratory studies described lethal and sublethal effects of neonicotinoids on the foraging behavior, and learning and memory abilities of bees, while no effects were observed in field studies at field-realistic dosages. The proposed risk assessment scheme for systemic compounds was shown to be applicable to assess the risk for side-effects of neonicotinoids as it considers the effect on different life stages and different levels of biological organization (organism versus colony). Future research studies should be conducted with field-realistic concentrations, relevant exposure and evaluation durations. Molecular markers may be used to improve risk assessment by a better understanding of the mode of action (interaction with receptors) of neonicotinoids in bees leading to the identification of environmentally safer compounds.
University of New South Wales1, National Health Service2, MedStar Washington Hospital Center3, Wake Forest University4, Claude Bernard University Lyon 15, Institut Gustave Roussy6, Mercy Medical Center (Baltimore, Maryland)7, St George's Hospital8, University of Barcelona9, Ghent University10, University of Würzburg11, University of Regensburg12, University of Texas MD Anderson Cancer Center13
TL;DR: The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years with Optimal cytoreduction achieves the best outcomes.
Abstract: Purpose Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. Patients and Methods A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International. Results Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), p...
Flanders Marine Institute1, Australian Museum2, University of New South Wales3, University of Southern Mississippi4, National Oceanography Centre, Southampton5, University of Hasselt6, WorldFish7, American Museum of Natural History8, San Diego State University9, Museum Victoria10, Natural History Museum11, Dowling College12, University of Hamburg13, University of Johannesburg14, James Cook University15, National Museum of Natural History16, National Taiwan Ocean University17, Scripps Institution of Oceanography18, National Oceanic and Atmospheric Administration19, University of Queensland20, University of Sassari21, Vrije Universiteit Brussel22, Université libre de Bruxelles23, Queensland Museum24, University of California, Merced25, Ghent University26, Naturalis27, Howard University28, University of Gothenburg29, California Academy of Sciences30, Florida Museum of Natural History31, Centre for Environment, Fisheries and Aquaculture Science32, Osaka University33, University of Santiago de Compostela34, University of Alaska Anchorage35, University of Málaga36, National Institute of Water and Atmospheric Research37, National University of Ireland, Galway38, University of Alaska Fairbanks39, Spanish National Research Council40, CABI41, University of Siegen42, Massey University43, University of Copenhagen44, Naturhistorisches Museum45, University of Washington46, Museum für Naturkunde47, Woods Hole Oceanographic Institution48, Western Washington University49, University of Bergen50, Nova Southeastern University51, Shirshov Institute of Oceanology52, National University of Singapore53, Shimane University54, Agnes Scott College55, University of the Ryukyus56, University of California, Davis57, Federal University of Paraná58, University of the Basque Country59, University of Veterinary Medicine Hanover60, Royal Belgian Institute of Natural Sciences61, Tel Aviv University62, Swedish Museum of Natural History63, Joint Nature Conservation Committee64, The Evergreen State College65, Estonian University of Life Sciences66, University of Maine67, Virginia Commonwealth University68, Trinity College, Dublin69, University of Auckland70
TL;DR: The first register of the marine species of the world is compiled and it is estimated that between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely.
Translational Genomics Research Institute1, Statens Serum Institut2, Technical University of Denmark3, Northern Arizona University4, University of Ljubljana5, Friedrich Loeffler Institute6, Ghent University7, ANSES8, Complutense University of Madrid9, Paris Diderot University10, University of Iowa11, University of Mississippi Medical Center12, Ontario Veterinary College13, Wenzhou Medical College14
TL;DR: The results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA, which appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance.
Abstract: Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCCmec) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCCmec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production. IMPORTANCE Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.
TL;DR: The fundamental mechanisms of WBAN including architecture and topology, wireless implant communication, low-power Medium Access Control (MAC) and routing protocols are reviewed and many useful solutions are discussed for each layer.
Abstract: Recent advances in microelectronics and integrated circuits, system-on-chip design, wireless communication and intelligent low-power sensors have allowed the realization of a Wireless Body Area Network (WBAN). A WBAN is a collection of low-power, miniaturized, invasive/non-invasive lightweight wireless sensor nodes that monitor the human body functions and the surrounding environment. In addition, it supports a number of innovative and interesting applications such as ubiquitous healthcare, entertainment, interactive gaming, and military applications. In this paper, the fundamental mechanisms of WBAN including architecture and topology, wireless implant communication, low-power Medium Access Control (MAC) and routing protocols are reviewed. A comprehensive study of the proposed technologies for WBAN at Physical (PHY), MAC, and Network layers is presented and many useful solutions are discussed for each layer. Finally, numerous WBAN applications are highlighted.
29 Mar 2012
TL;DR: In this article, the authors reported results from searches for the standard model Higgs boson in proton-proton collisions at square root(s) = 7 TeV in five decay modes: gamma pair, b-quark pair, tau lepton pair, W pair, and Z pair.
Abstract: Combined results are reported from searches for the standard model Higgs boson in proton-proton collisions at sqrt(s)=7 TeV in five Higgs boson decay modes: gamma pair, b-quark pair, tau lepton pair, W pair, and Z pair. The explored Higgs boson mass range is 110-600 GeV. The analysed data correspond to an integrated luminosity of 4.6-4.8 inverse femtobarns. The expected excluded mass range in the absence of the standard model Higgs boson is 118-543 GeV at 95% CL. The observed results exclude the standard model Higgs boson in the mass range 127-600 GeV at 95% CL, and in the mass range 129-525 GeV at 99% CL. An excess of events above the expected standard model background is observed at the low end of the explored mass range making the observed limits weaker than expected in the absence of a signal. The largest excess, with a local significance of 3.1 sigma, is observed for a Higgs boson mass hypothesis of 124 GeV. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-600 (110-145) GeV is estimated to be 1.5 sigma (2.1 sigma). More data are required to ascertain the origin of this excess.
TL;DR: This review presents recently gained insight on the distinct inflammasome types, their activation and effector mechanisms, and their modulation by microbial virulence factors and discusses recently gained knowledge on the role of deregulated inflammal activity in human autoinflammatory, autoimmune, and infectious diseases.
Abstract: Inflammasomes are a set of intracellular protein complexes that enable autocatalytic activation of inflammatory caspases, which drive host and immune responses by releasing cytokines and alarmins into circulation and by inducing pyroptosis, a proinflammatory cell death mode. The inflammasome type mediating these responses varies with the microbial pathogen or stress factor that poses a threat to the organism. Since the discovery that polymorphisms in inflammasome genes are linked to common autoimmune diseases and less frequent periodic fever syndromes, inflammasome signaling has been dissected at the molecular level. In this review, we present recently gained insight on the distinct inflammasome types, their activation and effector mechanisms, and their modulation by microbial virulence factors. In addition, we discuss recently gained knowledge on the role of deregulated inflammasome activity in human autoinflammatory, autoimmune, and infectious diseases.
TL;DR: Improved understanding of the epithelium's function in maintaining the integrity of the airways and its dysfunction in asthma has provided important mechanistic insight into how asthma is initiated and perpetuated and could provide a framework by which to select new therapeutic strategies that prevent exacerbations and alter the natural course of the disease.
Abstract: Asthma is a T lymphocyte-controlled disease of the airway wall caused by inflammation, overproduction of mucus and airway wall remodeling leading to bronchial hyperreactivity and airway obstruction. The airway epithelium is considered an essential controller of inflammatory, immune and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. Epithelial cells express pattern recognition receptors that detect environmental stimuli and secrete endogenous danger signals, thereby activating dendritic cells and bridging innate and adaptive immunity. Improved understanding of the epithelium's function in maintaining the integrity of the airways and its dysfunction in asthma has provided important mechanistic insight into how asthma is initiated and perpetuated and could provide a framework by which to select new therapeutic strategies that prevent exacerbations and alter the natural course of the disease.
TL;DR: The numerous advantages of the pig model for infectious disease research and vaccine development are highlighted and a few examples of human microbial infectious diseases for which the use of pigs as animal models has contributed to the acquisition of new knowledge are documented.
TL;DR: It is argued that the next generation of the FA model needs to more explicitly adopt a motivational perspective, one that is built around the organizing powers of goals and self-regulatory processes.
Abstract: Objective: The fear-avoidance (FA) model of chronic pain describes how individuals experiencing acute pain may become trapped into a vicious circle of chronic disability and suffering. We propose to extend the FA model by adopting a motivational perspective on chronic pain and disability. Methods: A narrative review. Results: There is ample evidence to support the validity of the FA model as originally formulated. There are, however, some key challenges that call for a next generation of the FA model. First, the FA model has its roots in psychopathology, and investigators will have to find a way to account for findings that do not easily fit within such framework. Second, the FA model needs to address the dynamics and complexities of disability and functional recovery. Third, the FA model should incorporate the idea that pain-related fear and avoidance occurs in a context of multiple and often competing personal goals. Discussion: To address these 3 key challenges, we argue that the next generation of the FA model needs to more explicitly adopt a motivational perspective, one that is built around the organizing powers of goals and self-regulatory processes. Using this framework, the FA model is recast as capturing the persistent but futile attempts to solve pain-related problems to protect and restore life goals.
TL;DR: Current understanding of organelle genome evolution in the green algae is summarized, genomic insights into the ecology of oceanic picoplanktonic prasinophytes, molecular mechanisms underlying the evolution of complexity in volvocine green algae, and the Evolution of genetic codes and the translational apparatus in green seaweeds are summarized.
Abstract: The green lineage (Viridiplantae) comprises the green algae and their descendants the land plants, and is one of the major groups of oxygenic photosynthetic eukaryotes. Current hypotheses posit the early divergence of two discrete clades from an ancestral green flagellate. One clade, the Chlorophyta, comprises the early diverging prasinophytes, which gave rise to the core chlorophytes. The other clade, the Streptophyta, includes the charophyte green algae from which the land plants evolved. Multi-marker and genome scale phylogenetic studies have greatly improved our understanding of broad-scale relationships of the green lineage, yet many questions persist, including the branching orders of the prasinophyte lineages, the relationships among core chlorophyte clades (Chlorodendrophyceae, Ulvophyceae, Trebouxiophyceae and Chlorophyceae), and the relationships among the streptophytes. Current phylogenetic hypotheses provide an evolutionary framework for molecular evolutionary studies and comparative genomics. This review summarizes our current understanding of organelle genome evolution in the green algae, genomic insights into the ecology of oceanic picoplanktonic prasinophytes, molecular mechanisms underlying the evolution of complexity in volvocine green algae, and the evolution of genetic codes and the translational apparatus in green seaweeds. Finally, we discuss molecular evolution in the streptophyte lineage, emphasizing the genetic facilitation of land plant origins.
Cincinnati Children's Hospital Medical Center1, Istituto Giannina Gaslini2, Hoffmann-La Roche3, University of Toronto4, Great Ormond Street Hospital5, Katholieke Universiteit Leuven6, Universidade Federal do Rio Grande do Sul7, National Health Service8, National Autonomous University of Mexico9, Charles University in Prague10, Autonomous University of Madrid11, Ghent University12, Utrecht University13, University of Padua14
TL;DR: Tocilizumab was efficacious in severe, persistent systemic JIA and adverse events were common and included infection, neutropenia, and increased aminotransferase levels.
Abstract: Background Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. Methods We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti–interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension. Results At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening...