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Showing papers by "University of Antwerp published in 2014"


Journal ArticleDOI
Stephan Ripke1, Stephan Ripke2, Benjamin M. Neale2, Benjamin M. Neale1  +351 moreInstitutions (102)
24 Jul 2014-Nature
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

6,809 citations


Journal ArticleDOI
TL;DR: It is proposed that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease.
Abstract: In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

2,581 citations


Journal ArticleDOI
12 Jun 2014-PLOS ONE
TL;DR: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimers disease.
Abstract: Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This s ...

1,518 citations


Journal ArticleDOI
TL;DR: The aim of this study is to incorporate support for multi-shell data into the CSD approach as well as to exploit the unique b-value dependencies of the different tissue types to estimate a multi-tissue ODF.

1,015 citations


Journal ArticleDOI
TL;DR: A new member of the family ofemiconducting transition metal dichalcogenides, rhenium disulphide (ReS2), where such variation is absent and bulk behaves as electronically and vibrationally decoupled monolayers stacked together.
Abstract: Monolayers of transition metal dichalcogenides have emerged as interesting two-dimensional materials. Here, the authors show that in a new member of this family of compounds, rhenium disulphide, the layers in the bulk are vibrationally and electronically decoupled, so that they behave almost as monolayers.

907 citations


Journal ArticleDOI
TL;DR: These data confirm the independent prognostic effect of CTC count on progression-free survival and overall survival and also improves the prognostication of metastatic breast cancer when added to full clinicopathological predictive models, whereas serum tumour markers do not.
Abstract: Summary Background We aimed to assess the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with metastatic breast cancer by undertaking a pooled analysis of individual patient data. Methods We contacted 51 European centres and asked them to provide reported and unreported anonymised data for individual patients with metastatic breast cancer who participated in studies between January, 2003, and July, 2012. Eligible studies had participants starting a new line of therapy, data for progression-free survival or overall survival, or both, and CTC quantification by the CellSearch method at baseline (before start of new treatment). We used Cox regression models, stratified by study, to establish the association between CTC count and progression-free survival and overall survival. We used the landmark method to assess the prognostic value of CTC and serum marker changes during treatment. We assessed the added value of CTCs or serum markers to prognostic clinicopathological models in a resampling procedure using likelihood ratio (LR) χ 2 statistics. Findings 17 centres provided data for 1944 eligible patients from 20 studies. 911 patients (46·9%) had a CTC count of 5 per 7·5 mL or higher at baseline, which was associated with decreased progression-free survival (hazard ratio [HR] 1·92, 95% CI 1·73–2·14, p Interpretation These data confirm the independent prognostic effect of CTC count on progression-free survival and overall survival. CTC count also improves the prognostication of metastatic breast cancer when added to full clinicopathological predictive models, whereas serum tumour markers do not. Funding Janssen Diagnostics, the Nuovo-Soldati foundation for cancer research.

630 citations


Journal ArticleDOI
TL;DR: Adherence to this principle and enhancement of the reliable practical use of the scale through continuing education of health professionals, standardisation across different settings, and consensus on methods to address confounders will maintain its role in clinical practice and research in the future.
Abstract: Since 1974, the Glasgow Coma Scale has provided a practical method for bedside assessment of impairment of conscious level, the clinical hallmark of acute brain injury. The scale was designed to be easy to use in clinical practice in general and specialist units and to replace previous ill-defined and inconsistent methods. 40 years later, the Glasgow Coma Scale has become an integral part of clinical practice and research worldwide. Findings using the scale have shown strong associations with those obtained by use of other early indices of severity and outcome. However, predictive statements should only be made in combination with other variables in a multivariate model. Individual patients are best described by the three components of the coma scale; whereas the derived total coma score should be used to characterise groups. Adherence to this principle and enhancement of the reliable practical use of the scale through continuing education of health professionals, standardisation across different settings, and consensus on methods to address confounders will maintain its role in clinical practice and research in the future.

611 citations


Journal ArticleDOI
TL;DR: It is reported that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM1-expressing cells.
Abstract: Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement. TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis. Whether and how TREM2 missense mutations affect TREM2 function is unclear. We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells. As a consequence of reduced shedding, TREM2 is virtually absent in the cerebrospinal fluid (CSF) and plasma of a patient with FTD-like syndrome. A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders.

603 citations


Journal ArticleDOI
TL;DR: The contribution of HPV prevalence in head and neck squamous cell carcinoma and in particular that of HPV16 in the oropharynx shows the potential benefit of prophylactic vaccines.
Abstract: Summary Background We aimed to provide updated information about the global estimates of attributable fraction and type distribution of human papillomavirus (HPV) in head and neck squamous cell carcinomas by doing a systematic review and meta-analysis. Methods We did a literature search on PubMed to identify studies that used PCR for detection of HPV DNA in head and neck squamous cell carcinomas with information about HPV genotype distribution. We included studies that tested 20 or more biopsies per cancer site and were published between July 15, 1990, and Feb 29, 2012. We collected information about sex, risk factors, HPV detection methods, and biomarkers of potentially HPV-induced carcinogenesis (E6/E7 mRNA and p16 INK4a ). If it was not possible to abstract the required information directly from the paper, we contacted the authors. We did a meta-analysis to produce pooled prevalence estimates including a meta-regression to explore sources of heterogeneity. Findings 148 studies were included, contributing data for 12 163 cases of head and neck squamous cell carcinoma from 44 countries. HPV DNA was detected in 3837 cases. HPV16 accounted for 82·2% (95% CI 77·7–86·4) of all HPV DNA positive cases. By cancer site, pooled HPV DNA prevalence estimates were 45·8% (95% CI 38·9–52·9) for oropharynx, 22·1% (16·4–28·3) for larynx (including hypopharynx), and 24·2% (18·7–30·2) for oral cavity. The percent positivity of p16 INK4a positive cases in HPV-positive oropharyngeal cancer cases was 86·7% (95% CI 79·2–92·9) and of E6/E7 mRNA positive cases was 86·9% (73·2–96·8). The estimate of HPV attributable fraction in oropharyngeal cancer defined by expression of positive cases of E6/E7 mRNA was 39·8% and of p16 INK4a was 39·7%. Of subsites, tonsils (53·9%, 95% CI 46·4–61·3) had the highest HPV DNA prevalence. HPV DNA prevalence varied significantly by anatomical site, geographic region, but not by sex or tobacco or alcohol consumption. Interpretation The contribution of HPV prevalence in head and neck squamous cell carcinoma and in particular that of HPV16 in the oropharynx shows the potential benefit of prophylactic vaccines. Funding European Commission.

574 citations


Journal ArticleDOI
S. Chatrchyan, Khachatryan1, Albert M. Sirunyan, Armen Tumasyan  +2384 moreInstitutions (207)
26 May 2014
TL;DR: In this paper, a description of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices is provided.
Abstract: A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For tt events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of p_T > 0.9GeV is 94% for pseudorapidities of |η| < 0.9 and 85% for 0.9 < |η| < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of p_T = 100GeV emitted at |η| < 1.4, the resolutions are approximately 2.8% in p_T, and respectively, 10μm and 30μm in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10–12μm in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung.

559 citations


Journal ArticleDOI
TL;DR: The clinical effectiveness of dendritic cell-based vaccine therapy in melanoma, prostate cancer, malignant glioma, and renal cell carcinoma is reviewed, and the most important lessons from almost two decades of clinical studies are summarized.
Abstract: Summary Since the mid-1990s, dendritic cells have been used in clinical trials as cellular mediators for therapeutic vaccination of patients with cancer. Dendritic cell-based immunotherapy is safe and can induce antitumour immunity, even in patients with advanced disease. However, clinical responses have been disappointing, with classic objective tumour response rates rarely exceeding 15%. Paradoxically, findings from emerging research indicate that dendritic cell-based vaccination might improve survival, advocating implementation of alternative endpoints to assess the true clinical potency of dendritic cell-based vaccination. We review the clinical effectiveness of dendritic cell-based vaccine therapy in melanoma, prostate cancer, malignant glioma, and renal cell carcinoma, and summarise the most important lessons from almost two decades of clinical studies of dendritic cell-based immunotherapy in these malignant disorders. We also address how the specialty is evolving, and which new therapeutic concepts are being translated into clinical trials to leverage the clinical effectiveness of dendritic cell-based cancer immunotherapy. Specifically, we discuss two main trends: the implementation of the next-generation dendritic cell vaccines that have improved immunogenicity, and the emerging paradigm of combination of dendritic cell vaccination with other cancer therapies.

Journal ArticleDOI
TL;DR: In a systematic review and meta-analysis, Giovanni Musso and colleagues examine the association between non-alcoholic fatty liver disease and chronic kidney disease and finds no clear link between the two.
Abstract: Background: Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. Methods and Findings: English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) ,60 ml/min/1.73 m 2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69– 2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65–1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58–4.05) and incidence (HR 2.12, 95% CI 1.42–3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14–8.61) and incidence (HR 3.29, 95% CI 2.30– 4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In crosssectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies. Conclusion: The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors’ Summary.

Journal ArticleDOI
TL;DR: In this paper, the authors presented the results of a project with the European Research Council and EPLANET (European Union) with the objective of supporting the development of a research network in the field of nuclear energy.
Abstract: Austrian Federal Ministry of Science and Research and the Austrian Science Fund; the Belgian Fonds de la Recherche Scientifique and Fonds voor Wetenschappelijk Onderzoek; the Brazilian Funding Agencies (CNPq, CAPES, FAPERJ, and FAPESP); the Bulgarian Ministry of Education and Science; CERN; the Chinese Academy of Sciences, Ministry of Science and Technology, and National Natural Science Foundation of China; the Colombian Funding Agency (COLCIENCIAS); the Croatian Ministry of Science, Education and Sport, and the Croatian Science Foundation; the Research Promotion Foundation, Cyprus; the Ministry of Education and Research, Recurrent Financing Contract No. SF0690030s09 and European Regional Development Fund, Estonia; the Academy of Finland, Finnish Ministry of Education and Culture, and Helsinki Institute of Physics; the Institut National de Physique Nucleaire et de Physique des Particules/CNRS and Commissariat a l’Energie Atomique et aux Energies Alternatives/CEA, France; the Bundesministerium fur Bildung und Forschung, Deutsche Forschungsgemeinschaft, and Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany; the General Secretariat for Research and Technology, Greece; the National Scientific Research Foundation and National Innovation Office, Hungary; the Department of Atomic Energy and the Department of Science and Technology, India; the Institute for Studies in Theoretical Physics and Mathematics, Iran; the Science Foundation, Ireland; the Istituto Nazionale di Fisica Nucleare, Italy; the Korean Ministry of Education, Science and Technology and the World Class University program of NRF, Republic of Korea; the Lithuanian Academy of Sciences; the Mexican Funding Agencies (CINVESTAV, CONACYT, SEP, and UASLP-FAI); the Ministry of Business, Innovation and Employment, New Zealand; the Pakistan Atomic Energy Commission; the Ministry of Science and Higher Education and the National Science Centre, Poland; the Fundacao para a Ciencia e a Tecnologia, Portugal; JINR, Dubna, the Ministry of Education and Science of the Russian Federation, the Federal Agency of Atomic Energy of the Russian Federation, Russian Academy of Sciences, and the Russian Foundation for Basic Research; the Ministry of Education, Science and Technological Development of Serbia; the Secretaria de Estado de Investigacion, Desarrollo e Innovacion and Programa Consolider-Ingenio 2010, Spain; the Swiss Funding Agencies (ETH Board, ETH Zurich, PSI, SNF, UniZH, Canton Zurich, and SER); the National Science Council, Taipei; the Thailand Center of Excellence in Physics, the Institute for the Promotion of Teaching Science and Technology of Thailand, Special Task Force for Activating Research and the National Science and Technology Development Agency of Thailand; the Scientific and Technical Research Council of Turkey and the Turkish Atomic Energy Authority; the Science and Technology Facilities Council, United Kingdom; the U.S. Department of Energy and the U.S. National Science Foundation.Individuals have received support from the Marie-Curie program and the European Research Council and EPLANET (European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation a la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Council of Science and Industrial Research, India; the Compagnia di San Paolo (Torino); the HOMING PLUS programme of Foundation for Polish Science, cofinanced by EU, Regional Development Fund; and the Thalis and Aristeia programmes cofinanced by EU-ESF and the Greek NSRF.

Journal ArticleDOI
TL;DR: In this paper, the diphoton decay mode of the recently discovered Higgs boson and measurement of some of its properties are reported using the entire dataset collected by the CMS experiment in proton-proton collisions during the 2011 and 2012 LHC running periods.
Abstract: Observation of the diphoton decay mode of the recently discovered Higgs boson and measurement of some of its properties are reported. The analysis uses the entire dataset collected by the CMS experiment in proton-proton collisions during the 2011 and 2012 LHC running periods. The data samples correspond to integrated luminosities of 5.1 inverse femtobarns at sqrt(s) = 7 TeV and 19.7 inverse femtobarns at 8 TeV. A clear signal is observed in the diphoton channel at a mass close to 125 GeV with a local significance of 5.7 sigma, where a significance of 5.2 sigma is expected for the standard model Higgs boson. The mass is measured to be 124.70 +/- 0.34 GeV = 124.70 +/- 0.31 (stat) +/- 0.15 (syst) GeV, and the best-fit signal strength relative to the standard model prediction is 1.14 +0.26/-0.23 = 1.14 +/- 0.21 (stat) +0.09/-0.05 (syst) +0.13/-0.09 (theo). Additional measurements include the signal strength modifiers associated with different production mechanisms, and hypothesis tests between spin-0 and spin-2 models.


Journal ArticleDOI
TL;DR: In this article, the abundance and structure of WDM haloes and subhaloes on these scales were investigated using high resolution cosmological N-body simulations of galactic haloes of mass similar to the Milky Way's.
Abstract: Well-motivated elementary particle candidates for the dark matter, such as the sterile neutrino, behave as warm dark matter (WDM). For particle masses of order a keV, free streaming produces a cutoff in the linear fluctuation power spectrum at a scale corresponding to dwarf galaxies. We investigate the abundance and structure of WDM haloes and subhaloes on these scales using high resolution cosmological N-body simulations of galactic haloes of mass similar to the Milky Way’s. On scales larger than the free-streaming cutoff, the initial conditions have the same power spectrum and phases as one of the cold dark matter (CDM) haloes previously simulated by Springel et al as part of the Virgo consortium Aquarius project. We have simulated four haloes with WDM particle masses in the range 1.4 − 2.3 keV and, for one case, we have carried out further simulations at varying resolution. N-body simulations in which the power spectrum cutoff is resolved are known to undergo artificial fragmentation in filaments producing spurious clumps which, for small masses (< 10 7 M ⊙ in our case) outnumber genuine haloes. We have developed a robust algorithm to identify these spurious objects and remove them from our halo catalogues. We find that the WDM subhalo mass function is suppressed by well over an order magnitude relative to the CDM case for masses < 10 9 M ⊙ . Requiring that there should be at least as many subhaloes as there are observed satellites in the Milky Way leads to a conservative lower limit to the (thermal equivalent) WDM particle mass of ∼ 1.5keV. WDM haloes and subhaloes have cuspy density distributions that are well described by NFW or Einasto profiles. Their central densities are lower for lower WDM particle masses and none of the models we have considered suffer from the “too big to fail” problem recently highlighted by Boylan-Kolchin et al.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the effects of ash on the burned ecosystem, especially when transported by wind or water, and investigated its control on water and soil losses at slope and catchment scales, and examined its role in the C cycle.


Journal ArticleDOI
TL;DR: This review of literature and expert opinion aims to provide medical guidelines for care of individuals with Loeys–Dietz syndrome.

Journal ArticleDOI
TL;DR: Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI, in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials.
Abstract: BACKGROUND Progesterone has been associated with robust positive effects in animal models of traumatic brain injury (TBI) and with clinical benefits in two phase 2 randomized, controlled trials. We investigated the efficacy and safety of progesterone in a large, prospective, phase 3 randomized clinical trial. METHODS We conducted a multinational placebo-controlled trial, in which 1195 patients, 16 to 70 years of age, with severe TBI (Glasgow Coma Scale score, ≤8 [on a scale of 3 to 15, with lower scores indicating a reduced level of consciousness] and at least one reactive pupil) were randomly assigned to receive progesterone or placebo. Dosing began within 8 hours after injury and continued for 120 hours. The primary efficacy end point was the Glasgow Outcome Scale score at 6 months after the injury. RESULTS Proportional-odds analysis with covariate adjustment showed no treatment effect of progesterone as compared with placebo (odds ratio, 0.96; confidence interval, 0.77 to 1.18). The proportion of patients with a favorable outcome on the Glasgow Outcome Scale (good recovery or moderate disability) was 50.4% with progesterone, as compared with 50.5% with placebo. Mortality was similar in the two groups. No relevant safety differences were noted between progesterone and placebo. CONCLUSIONS Primary and secondary efficacy analyses showed no clinical benefit of progesterone in patients with severe TBI. These data stand in contrast to the robust preclinical data and results of early single-center trials that provided the impetus to initiate phase 3 trials. (Funded by BHR Pharma; SYNAPSE ClinicalTrials.gov number, NCT01143064.)

Journal ArticleDOI
TL;DR: In this paper, the authors review the state of citizen science in a hydrological context and explore the potential for citizen science to complement more traditional ways of scientific data collection and knowledge generation.
Abstract: The participation of the general public in the research design, data collection and interpretation process together with scientists is often referred to as citizen science. While citizen science itself has existed since the start of scientific practice, developments in sensing technology, data processing and visualisation, and communication of ideas and results, are creating a wide range of new opportunities for public participation in scientific research. This paper reviews the state of citizen science in a hydrological context and explores the potential of citizen science to complement more traditional ways of scientific data collection and knowledge generation for hydrological sciences and water resources management. Although hydrological data collection often involves advanced technology, the advent of robust, cheap and low-maintenance sensing equipment provides unprecedented opportunities for data collection in a citizen science context. These data have a significant potential to create new hydrological knowledge, especially in relation to the characterisation of process heterogeneity, remote regions, and human impacts on the water cycle. However, the nature and quality of data collected in citizen science experiments is potentially very different from those of traditional monitoring networks. This poses challenges in terms of their processing, interpretation, and use, especially with regard to assimilation of traditional knowledge, the quantification of uncertainties, and their role in decision support. It also requires care in designing citizen science projects such that the generated data complement optimally other available knowledge. Lastly, we reflect on the challenges and opportunities in the integration of hydrologically-oriented citizen science in water resources management, the role of scientific knowledge in the decision-making process, and the potential contestation to established community institutions posed by co-generation of new knowledge.

Journal ArticleDOI
TL;DR: In this paper, a synthesis of findings from 92 forests in different climate zones reveals that nutrient availability plays a crucial role in determining forest carbon balance, primarily through its influence on respiration rates.
Abstract: A synthesis of findings from 92 forests in different climate zones reveals that nutrient availability plays a crucial role in determining forest carbon balance, primarily through its influence on respiration rates. These findings challenge the validity of assumptions used in most global coupled carbon-cycle climate models.

Journal ArticleDOI
TL;DR: A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early-stage disease and locally advanced disease.

Journal ArticleDOI
23 Dec 2014-PLOS ONE
TL;DR: A modified generic scoring system with high reproducibility that is applicable for different rodent models and for all stages of NAFLD etiology is established.
Abstract: Results: The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high for the analysis of macrovesicular steatosis and microvesicular steatosis (ICC50.784 and 0.776, all p,0.001, respectively) and moderate for the analysis of hypertrophy and inflammation (ICC50.685 and 0.650, all p,0.001, respectively). The intra-observer reproducibility between the different observations of one observer was high for the analysis of macrovesicular steatosis, microvesicular steatosis and hypertrophy (ICC50.871, 0.871 and 0.896, all p,0.001, respectively) and very high for the analysis of inflammation (ICC50.931, p,0.001). Conclusions: We established a simple NAFLD scoring system with high reproducibility that is applicable for different rodent models and for all stages of NAFLD etiology. Background and aims: The recently developed histological scoring system for non-alcoholic fatty liver disease (NAFLD) by the NASH Clinical Research Network (NASH-CRN) has been widely used in clinical settings, but is increasingly employed in preclinical research as well. However, it has not been systematically analyzed whether the human scoring system can directly be converted to preclinical rodent models. To analyze this, we systematically compared human NAFLD liver pathology, using human liver biopsies, with liver pathology of several NAFLD mouse models. Based upon the features pertaining to mouse NAFLD, we aimed at establishing a modified generic scoring system that is applicable to broad spectrum of rodent models. Copyright: Methods: The histopathology of NAFLD was analyzed in several different mouse models of NAFLD to define generic criteria for histological assessment (preclinical scoring system). For validation of this scoring system, 36 slides of mouse livers, covering the whole spectrum of NAFLD, were blindly analyzed by ten observers. Additionally, the livers were blindly scored by one observer during two separate assessments longer than 3 months apart.

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TL;DR: More data on temporal trends of BDE and HBCD concentrations in a variety of matrices and locations are needed before the current status of these compounds can be fully assessed, and the impact of regulation and changing usage patterns among different flame retardants determined.

Journal ArticleDOI
Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam  +2121 moreInstitutions (139)
TL;DR: In this paper, searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and W, Z, and Higgs bosons are presented.
Abstract: Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and W, Z, and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy sqrt(s) = 8 TeV with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 inverse femtobarns. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 GeV, and sleptons up to 260 GeV, depending on the model details.

Journal ArticleDOI
S. Chatrchyan1, Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1  +2280 moreInstitutions (177)
TL;DR: In this paper, a search for a standard model Higgs boson decaying into a pair of tau leptons is performed using events recorded by the CMS experiment at the LHC in 2011 and 2012.
Abstract: A search for a standard model Higgs boson decaying into a pair of tau leptons is performed using events recorded by the CMS experiment at the LHC in 2011 and 2012. The dataset corresponds to an integrated luminosity of 4.9 inverse femtobarns at a centre-of-mass energy of 7 TeV and 19.7 inverse femtobarns at 8 TeV. Each tau lepton decays hadronically or leptonically to an electron or a muon, leading to six different final states for the tau-lepton pair, all considered in this analysis. An excess of events is observed over the expected background contributions, with a local significance larger than 3 standard deviations for m[H] values between 115 and 130 GeV. The best fit of the observed H to tau tau signal cross section for m[H] = 125 GeV is 0.78 +- 0.27 times the standard model expectation. These observations constitute evidence for the 125 GeV Higgs boson decaying to a pair of tau leptons.

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TL;DR: A role for multiple biomarker measurements in TBI research is supported and analysis of both UCH-L1 and GFAP would be superior to analysis of each alone for the diagnosis and prognosis of TBI.
Abstract: Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and...

Journal ArticleDOI
TL;DR: In this article, a zero-dimensional kinetic model of CO2 splitting in non-equilibrium plasmas is presented, which includes a description of the CO2 vibrational kinetics (25 vibrational levels up to the dissociation limit of the molecule), taking into account state specific VT and VV relaxation reactions and the effect of vibrational excitation on other chemical reactions.
Abstract: We present a zero-dimensional kinetic model of CO2 splitting in non-equilibrium plasmas. The model includes a description of the CO2 vibrational kinetics (25 vibrational levels up to the dissociation limit of the molecule), taking into account state-specific VT and VV relaxation reactions and the effect of vibrational excitation on other chemical reactions. The model is applied to study the reaction kinetics of CO2 splitting in an atmospheric-pressure dielectric barrier discharge (DBD) and in a moderate-pressure microwave discharge. The model results are in qualitative agreement with published experimental works. We show that the CO2 conversion and its energy efficiency are very different in these two types of discharges, which reflects the important dissociation mechanisms involved. In the microwave discharge, excitation of the vibrational levels promotes efficient dissociation when the specific energy input is higher than a critical value (2.0 eV/molecule under the conditions examined). The calculated energy efficiency of the process has a maximum of 23%. In the DBD, vibrationally excited levels do not contribute significantly to the dissociation of CO2 and the calculated energy efficiency of the process is much lower (5%).

Journal ArticleDOI
20 Jun 2014-Science
TL;DR: An extensive atomic and nanoscale characterization of these systems using direct imaging and wave scattering methods is presented, showing how the interfacial self-assembly and oriented attachment of nanocrystals results in 2D metal chalcogenide semiconductors with a honeycomb superlattice.
Abstract: Oriented attachment of synthetic semiconductor nanocrystals is emerging as a route for obtaining new semiconductors that can have Dirac-type electronic bands such as graphene, but also strong spin-orbit coupling. The two-dimensional (2D) assembly geometry will require both atomic coherence and long-range periodicity of the superlattices. We show how the interfacial self-assembly and oriented attachment of nanocrystals results in 2D metal chalcogenide semiconductors with a honeycomb superlattice. We present an extensive atomic and nanoscale characterization of these systems using direct imaging and wave scattering methods. The honeycomb superlattices are atomically coherent and have an octahedral symmetry that is buckled; the nanocrystals occupy two parallel planes. Considerable necking and large-scale atomic motion occurred during the attachment process.