Showing papers by "University of Florence published in 2013"
Jean-Charles Lambert1, Jean-Charles Lambert2, Jean-Charles Lambert3, Carla A. Ibrahim-Verbaas4 +212 more•Institutions (75)
TL;DR: In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Abstract: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
3,726 citations
University of Edinburgh1, University of Calgary2, Medical University of Graz3, The George Institute for Global Health4, University of Cambridge5, VU University Amsterdam6, University of British Columbia7, Sunnybrook Health Sciences Centre8, German Center for Neurodegenerative Diseases9, Paris Diderot University10, University of California, Davis11, Radboud University Nijmegen Medical Centre12, Ludwig Maximilian University of Munich13, University College London14, Harvard University15, University of Western Ontario16, The Chinese University of Hong Kong17, Maastricht University18, University of Florence19, Otto-von-Guericke University Magdeburg20, Newcastle University21, National University of Singapore22, Leiden University Medical Center23, University of Saint Mary24
TL;DR: This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
Abstract: Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
3,691 citations
Radboud University Nijmegen Medical Centre1, University of Michigan2, Radboud University Nijmegen3, University of Toronto4, McGill University5, University of Basel6, University of Florence7, Auckland City Hospital8, University of Pittsburgh9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, National Health Service26, University of Colorado Denver27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, Rutgers University31, Thomas Jefferson University32, Amgen33, University of Toledo34, Boston University35, Medical University of South Carolina36, University of Pennsylvania37, Northwestern University38
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
2,743 citations
Radboud University Nijmegen1, University of Michigan2, University of Toronto3, McGill University4, University of Basel5, University of Florence6, Auckland City Hospital7, University of Pittsburgh8, Complutense University of Madrid9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, Amgen26, University of Colorado Denver27, Medical College of Wisconsin28, University of Alabama at Birmingham29, National Health Service30, University of Manchester31, Rutgers University32, Thomas Jefferson University33, University of Toledo34, Boston University35, University of Pennsylvania36, Medical University of South Carolina37, Northwestern University38, University of Western Ontario39
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud9s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
1,899 citations
TL;DR: A metabolic pathway whereby Trp metabolites from the microbiota balance mucosal reactivity in mice is described, whereby highly adaptive lactobacilli are expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde-that contributes to AhR-dependent Il22 transcription.
1,540 citations
TL;DR: General classes of direct value comparison, coupling real and modelled values, preserving data patterns, indirect metrics based on parameter values, and data transformations are discussed.
Abstract: In order to use environmental models effectively for management and decision-making, it is vital to establish an appropriate level of confidence in their performance. This paper reviews techniques available across various fields for characterising the performance of environmental models with focus on numerical, graphical and qualitative methods. General classes of direct value comparison, coupling real and modelled values, preserving data patterns, indirect metrics based on parameter values, and data transformations are discussed. In practice environmental modelling requires the use and implementation of workflows that combine several methods, tailored to the model purpose and dependent upon the data and information available. A five-step procedure for performance evaluation of models is suggested, with the key elements including: (i) (re)assessment of the model's aim, scale and scope; (ii) characterisation of the data for calibration and testing; (iii) visual and other analysis to detect under- or non-modelled behaviour and to gain an overview of overall performance; (iv) selection of basic performance criteria; and (v) consideration of more advanced methods to handle problems such as systematic divergence between modelled and observed values.
1,207 citations
1,090 citations
Tel Aviv University1, Ludwig Maximilian University of Munich2, Hebrew University of Jerusalem3, Erasmus University Rotterdam4, Sapienza University of Rome5, University of Helsinki6, Semmelweis University7, Boston Children's Hospital8, University of Copenhagen9, University of Toronto10, University of Florence11, Jagiellonian University12, University of Barcelona13, University of Naples Federico II14, University of Paris15, University of Edinburgh16
TL;DR: These revised Porto criteria for the diagnosis of P IBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.
Abstract: Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. Methods: We aimed to revise the original Porto criteria using an evidencebased approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. Results: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy.
929 citations
Federal Urdu University1, Woods Hole Oceanographic Institution2, Columbia University3, Addis Ababa University4, Indian Institute of Tropical Meteorology5, University of Trieste6, Swiss Federal Institute for Forest, Snow and Landscape Research7, University of Bergen8, University of Montpellier9, Austral University of Chile10, University of Chile11, Australian Antarctic Division12, University of Tasmania13, National Oceanic and Atmospheric Administration14, University of Mainz15, Xishuangbanna Tropical Botanical Garden16, Nepal Academy of Science and Technology17, Chinese Academy of Sciences18, University of Melbourne19, Complutense University of Madrid20, Université catholique de Louvain21, University of the Witwatersrand22, Hydrologic Research Center23, University of Bern24, University of Helsinki25, Northern Arizona University26, Fukushima University27, Stockholm University28, Université Paris-Saclay29, National Institute of Water and Atmospheric Research30, University of Giessen31, Swansea University32, Desert Research Institute33, National Scientific and Technical Research Council34, British Antarctic Survey35, Nagoya University36, University of Brighton37, Florida State University38, Alfred Wegener Institute for Polar and Marine Research39, University of Exeter40, University of New South Wales41, Centro de Estudios Científicos42, University of Florence43, University of Texas at Austin44, Russian Academy of Sciences45, University of Washington46, National Centre for Antarctic and Ocean Research47, University of Arizona48, Ghent University49, University of Ottawa50, University of Copenhagen51, University of Colorado Boulder52, Shinshu University53
TL;DR: The authors reconstructed past temperatures for seven continental-scale regions during the past one to two millennia and found that the most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century.
Abstract: Past global climate changes had strong regional expression To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years
885 citations
TL;DR: In this paper, the authors introduce the concept of rogue waves, which is the name given by oceanographers to isolated large amplitude waves, that occur more frequently than expected for normal, Gaussian distributed, statistical events.
851 citations
TL;DR: Cancer cells develop anoikis resistance due to several mechanisms, including change in integrins' repertoire allowing them to grow in different niches, activation of a plethora of inside-out pro-survival signals as well as leading to metabolic deregulations of cancer cells.
TL;DR: Revised criteria are proposed for pediatric acute disseminated encephalomyelitis, pediatric clinically isolated syndrome, pediatric neuromyELitis optica and pediatric MS to incorporate advances in delineating the clinical and neuroradiologic features of these disorders.
Abstract: Background: There has been tremendous growth in research in pediatric multiple sclerosis (MS) and immune mediated central nervous system demyelinating disorders since operational definitions for these conditions were first proposed in 2007. Further, the International Pediatric Multiple Sclerosis Study Group (IPMSSG), which proposed the criteria, has expanded substantially in membership and in its international scope. Objective: The purpose of this review is to revise the 2007 definitions in order to incorporate advances in delineating the clinical and neuroradiologic features of these disorders. Methods: Through a consensus process, in which input was sought from the 150 members of the Study Group, criteria were drafted, revised and finalized. Final approval was sought through a web survey. Results: Revised criteria are proposed for pediatric acute disseminated encephalomyelitis, pediatric clinically isolated syndrome, pediatric neuromyelitis optica and pediatric MS. These criteria were approved by 93% or more of the 56 Study Group members who responded to the final survey. Conclusions: These definitions are proposed for clinical and research purposes. Their utility will depend on the outcomes of their application in prospective research.
Aix-Marseille University1, Scripps Health2, Gyeongsang National University3, University of Florida4, Columbia University5, National Health Service6, University of Tübingen7, Medical University of Vienna8, Medical University of Graz9, Duke University10, Harvard University11, MedStar Washington Hospital Center12, University of Patras13, University of Florence14, University of Geneva15, University of Freiburg16, Ludwig Maximilian University of Munich17
TL;DR: An updated consensus document reviews the available evidence and proposes cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy and proposes a therapeutic window concept for P2Y12 inhibitor therapy.
TL;DR: In this article, the authors proposed a set of recommendations specifically aimed at subsolid nodules, which are based on the original Fleischner Society guidelines for incidentally detected solid nodules.
Abstract: This report is to complement the original Fleischner Society recommendations for incidentally detected solid nodules by proposing a set of recommendations specifically aimed at subsolid nodules. The development of a standardized approach to the interpretation and management of subsolid nodules remains critically important given that peripheral adenocarcinomas represent the most common type of lung cancer, with evidence of increasing frequency. Following an initial consideration of appropriate terminology to describe subsolid nodules and a brief review of the new classification system for peripheral lung adenocarcinomas sponsored by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), six specific recommendations were made, three with regard to solitary subsolid nodules and three with regard to multiple subsolid nodules. Each recommendation is followed first by the rationales underlying the recommendation and then by specific pertinent remarks. Finally, issues for which future research is needed are discussed. The recommendations are the result of careful review of the literature now available regarding subsolid nodules. Given the complexity of these lesions, the current recommendations are more varied than the original Fleischner Society guidelines for solid nodules. It cannot be overemphasized that these guidelines must be interpreted in light of an individual's clinical history. Given the frequency with which subsolid nodules are encountered in daily clinical practice, and notwithstanding continuing controversy on many of these issues, it is anticipated that further refinements and modifications to these recommendations will be forthcoming as information continues to emerge from ongoing research.
Polytechnic University of Catalonia1, University of Twente2, University of Milan3, University of Salerno4, Centre national de la recherche scientifique5, Aristotle University of Thessaloniki6, University of Florence7, Transport Research Laboratory8, Technical University of Madrid9, Golder Associates10
TL;DR: In this article, the authors present recommended methodologies for the quantitative analysis of landslide hazard, vulnerability and risk at different spatial scales (site-specific, local, regional and national), as well as for the verification and validation of the results.
Abstract: This paper presents recommended methodologies for the quantitative analysis of landslide hazard, vulnerability and risk at different spatial scales (site-specific, local, regional and national), as well as for the verification and validation of the results. The methodologies described focus on the evaluation of the probabilities of occurrence of different landslide types with certain characteristics. Methods used to determine the spatial distribution of landslide intensity, the characterisation of the elements at risk, the assessment of the potential degree of damage and the quantification of the vulnerability of the elements at risk, and those used to perform the quantitative risk analysis are also described. The paper is intended for use by scientists and practising engineers, geologists and other landslide experts.
TL;DR: The results provide the first analysis of the global conservation status and distribution patterns of reptiles and the threats affecting them, highlighting conservation priorities and knowledge gaps which need to be addressed urgently to ensure the continued survival of the world’s reptiles.
TL;DR: In this paper, the results of the four LEP experiments were combined to determine fundamental properties of the W boson and the electroweak theory, including the branching fraction of W and the trilinear gauge-boson self-couplings.
TL;DR: In this article, a detailed description of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson.
Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.
Leiden University1, University of Helsinki2, University of Bonn3, University of Copenhagen4, Newcastle University5, Leipzig University6, Cardiff University7, University of Florence8, University of London9, University of Manchester10, Karolinska Institutet11, University of the East12, Radboud University Nijmegen13, Pierre-and-Marie-Curie University14, Katholieke Universiteit Leuven15, Imperial College London16, University of Düsseldorf17, Helsinki University Central Hospital18
TL;DR: The guidelines described in this paper may be helpful for the appropriate management of families with LS and Prospective controlled studies should be undertaken to improve further the care of these families.
Abstract: Lynch syndrome (LS) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. In 2007, a group of European experts (the Mallorca group) published guidelines for the clinical management of LS. Since then substantial new information has become available necessitating an update of the guidelines. In 2011 and 2012 workshops were organised in Palma de Mallorca. A total of 35 specialists from 13 countries participated in the meetings. The first step was to formulate important clinical questions. Then a systematic literature search was performed using the Pubmed database and manual searches of relevant articles. During the workshops the outcome of the literature search was discussed in detail. The guidelines described in this paper may be helpful for the appropriate management of families with LS. Prospective controlled studies should be undertaken to improve further the care of these families.
TL;DR: Mutational profiling for ASXL1, EZH2, SRSF2 and IDH identifies PMF patients who are at risk for premature death or leukemic transformation.
Abstract: Patient outcome in primary myelofibrosis (PMF) is significantly influenced by karyotype. We studied 879 PMF patients to determine the individual and combinatorial prognostic relevance of somatic mutations. Analysis was performed in 483 European patients and the seminal observations were validated in 396 Mayo Clinic patients. Samples from the European cohort, collected at time of diagnosis, were analyzed for mutations in ASXL1, SRSF2, EZH2, TET2, DNMT3A, CBL, IDH1, IDH2, MPL and JAK2. Of these, ASXL1, SRSF2 and EZH2 mutations inter-independently predicted shortened survival. However, only ASXL1 mutations (HR: 2.02; P<0.001) remained significant in the context of the International Prognostic Scoring System (IPSS). These observations were validated in the Mayo Clinic cohort where mutation and survival analyses were performed from time of referral. ASXL1, SRSF2 and EZH2 mutations were independently associated with poor survival, but only ASXL1 mutations held their prognostic relevance (HR: 1.4; P=0.04) independent of the Dynamic IPSS (DIPSS)-plus model, which incorporates cytogenetic risk. In the European cohort, leukemia-free survival was negatively affected by IDH1/2, SRSF2 and ASXL1 mutations and in the Mayo cohort by IDH1 and SRSF2 mutations. Mutational profiling for ASXL1, EZH2, SRSF2 and IDH identifies PMF patients who are at risk for premature death or leukemic transformation.
Mario Negri Institute for Pharmacological Research1, Catholic University of the Sacred Heart2, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico3, Sapienza University of Rome4, Vita-Salute San Raffaele University5, University of Eastern Piedmont6, University of Messina7, Casa Sollievo della Sofferenza8, University of Padua9, Marche Polytechnic University10, University of Florence11
TL;DR: In patients with polycythemia vera, those with a hematocrit target of less than 45% had a significantly lower rate of cardiovascular death and major thrombosis than did those with an intended target of 45 to 50%.
Abstract: A b s t r ac t Background Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial. Methods We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit, <45%) (low-hematocrit group) or less intensive treatment (target hematocrit, 45 to 50%) (high-hematocrit group). The primary composite end point was the time until death from cardiovascular causes or major thrombotic events. The secondary end points were cardiovascular events, cardiovascular hospitalizations, incidence of cancer, progression to myelofibrosis, myelodysplasia or leukemic transformation, and hemorrhage. An intention-to-treat analysis was performed. Results After a median follow-up of 31 months, the primary end point was recorded in 5 of 182 patients in the low-hematocrit group (2.7%) and 18 of 183 patients in the highhematocrit group (9.8%) (hazard ratio in the high-hematocrit group, 3.91; 95% confidence interval [CI], 1.45 to 10.53; P = 0.007). The primary end point plus superficial-vein thrombosis occurred in 4.4% of patients in the low-hematocrit group, as compared with 10.9% in the high-hematocrit group (hazard ratio, 2.69; 95% CI, 1.19 to 6.12; P = 0.02). Progression to myelofibrosis, myelodysplasia or leukemic transformation, and bleeding were observed in 6, 2, and 2 patients, respectively, in the low-hematocrit group, as compared with 2, 1, and 5 patients, respectively, in the high-hematocrit group. There was no significant between-group difference in the rate of adverse events. Conclusions In patients with polycythemia vera, those with a hematocrit target of less than 45% had a significantly lower rate of cardiovascular death and major thrombosis than did those with a hematocrit target of 45 to 50%. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT01645124, and EudraCT number, 2007–006694-91.)
Journal Article•
TL;DR: The results of the Forest Resources Assessment 2000 carried out by FAO are synthetically presented and discussed in this paper, which shows a general deceleration of the rate of net deforestation, that currently involves around 9 million hectares every year.
Abstract: The results of the Forest Resources Assessment 2000 carried out by FAO are synthetically presented and discussed. The world forest coverage is estimated equal to 38.6 million km 2 . The comparison of the estimates from the period 1990-2000 with those from the period 1980-1990 points out a certain general deceleration of the rate of net deforestation, that currently involves around 9 million hectares every year. However, the annua1 loss of tropical forests is still very large, while temperate and borea1 forests are in expansion. Overall, FRA2000 produced a relevant effort to compensate the existing technical, institutional and financial constraints and shortcomings for monitoring the world forest resources. The need to increase the quality and the frequency of forest surveys, both at national and international levels, s t a stands as a major issue to cope with.
TL;DR: The SARIMA model coupled with a Kalman filter is the most accurate model; however, the proposed seasonal support vector regressor turns out to be highly competitive when performing forecasts during the most congested periods.
Abstract: The literature on short-term traffic flow forecasting has undergone great development recently. Many works, describing a wide variety of different approaches, which very often share similar features and ideas, have been published. However, publications presenting new prediction algorithms usually employ different settings, data sets, and performance measurements, making it difficult to infer a clear picture of the advantages and limitations of each model. The aim of this paper is twofold. First, we review existing approaches to short-term traffic flow forecasting methods under the common view of probabilistic graphical models, presenting an extensive experimental comparison, which proposes a common baseline for their performance analysis and provides the infrastructure to operate on a publicly available data set. Second, we present two new support vector regression models, which are specifically devised to benefit from typical traffic flow seasonality and are shown to represent an interesting compromise between prediction accuracy and computational efficiency. The SARIMA model coupled with a Kalman filter is the most accurate model; however, the proposed seasonal support vector regressor turns out to be highly competitive when performing forecasts during the most congested periods.
TL;DR: In this paper, two-particle angular correlations for charged particles emitted in pPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV are presented.
Max Planck Society1, Chinese Academy of Sciences2, University of Tübingen3, Emory University4, École pratique des hautes études5, University of Florence6, University of Mainz7, University of Bonn8, University of Siena9, University of Pisa10, Masaryk University11, Academy of Sciences of the Czech Republic12, Broad Institute13, Harvard University14
TL;DR: This work uses mitochondrial genome sequences from ten securely dated ancient modern humans spanning 40,000 years as calibration points for the mitochondrial clock, thus yielding a direct estimate of the mitochondrial substitution rate and implies a separation of non-Africans from the most closely related sub-Saharan African mitochondrial DNAs that occurred less than 62-95 kya.
TL;DR: In multivariable analysis, survival for the entire study cohort was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model delineated risk groups with median survivals of 10.9–27.8 years.
Abstract: Under the auspices of an International Working Group, seven centers submitted diagnostic and follow-up information on 1545 patients with World Health Organization-defined polycythemia vera (PV). At diagnosis, median age was 61 years (51% females); thrombocytosis and venous thrombosis were more frequent in women and arterial thrombosis and abnormal karyotype in men. Considering patients from the center with the most mature follow-up information (n=337 with 44% of patients followed to death), median survival (14.1 years) was significantly worse than that of the age- and sex-matched US population (P<0.001). In multivariable analysis, survival for the entire study cohort (n=1545) was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model that included the first three parameters delineated risk groups with median survivals of 10.9–27.8 years (hazard ratio (HR), 10.7; 95% confidence interval (CI): 7.7–15.0). Pruritus was identified as a favorable risk factor for survival. Cumulative hazard of leukemic transformation, with death as a competing risk, was 2.3% at 10 years and 5.5% at 15 years; risk factors included older age, abnormal karyotype and leukocytes ⩾15 × 109/l. Leukemic transformation was associated with treatment exposure to pipobroman or P32/chlorambucil. We found no association between leukemic transformation and hydroxyurea or busulfan use.
University of Paris1, University Hospital of Wales2, University of Copenhagen3, University of Amsterdam4, Third Military Medical University5, National University of Cordoba6, King Khalid University7, Harvard University8, Brigham and Women's Hospital9, University of Szeged10, Erasmus University Rotterdam11, Aarhus University12, University of Florence13, University of Colorado Denver14, University of Catania15, University of California, Berkeley16, University of South Australia17, University of Iceland18, French Institute of Health and Medical Research19
TL;DR: Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia, and whether weight normalization could improve sperm parameters should be evaluated further.
Abstract: BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.
Tuscia University1, Institut national de la recherche agronomique2, University of Florence3, Forest Research Institute4, Finnish Forest Research Institute5, Mendel University6, University of Natural Resources and Life Sciences, Vienna7, Norwegian Forest and Landscape Institute8, University of Extremadura9, University of West Hungary10, Forestry Commission11, University of Aberdeen12, Swedish University of Agricultural Sciences13
TL;DR: A large database of invasive forest pathogens was developed to investigate the patterns and determinants of invasion in Europe, finding thatEradication seems impossible, and prevention seems the only reliable measure, although this will be difficult in the face of global mobility.
Abstract: A large database of invasive forest pathogens (IFPs) was developed to investigate the patterns and determinants of invasion in Europe. Detailed taxonomic and biological information on the invasive species was combined with country-specific data on land use, climate, and the time since invasion to identify the determinants of invasiveness, and to differentiate the class of environments which share territorial and climate features associated with a susceptibility to invasion. IFPs increased exponentially in the last four decades. Until 1919, IFPs already present moved across Europe. Then, new IFPs were introduced mainly from North America, and recently from Asia. Hybrid pathogens also appeared. Countries with a wider range of environments, higher human impact or international trade hosted more IFPs. Rainfall influenced the diffusion rates. Environmental conditions of the new and original ranges and systematic and ecological attributes affected invasiveness. Further spread of established IFPs is expected in countries that have experienced commercial isolation in the recent past. Densely populated countries with high environmental diversity may be the weakest links in attempts to prevent new arrivals. Tight coordination of actions against new arrivals is needed. Eradication seems impossible, and prevention seems the only reliable measure, although this will be difficult in the face of global mobility.
University of Milan1, Spanish National Research Council2, University of Parma3, University of Bern4, University of Helsinki5, University of Düsseldorf6, Bangor University7, University of Kiel8, University of Natural Resources and Life Sciences, Vienna9, National University of Ireland, Galway10, University of Florence11, University College Dublin12, University of Milano-Bicocca13, Utrecht University14, Joseph Fourier University15, University of Seville16, University of Leeds17, Maynooth University18, Claude Bernard University Lyon 119, Université de Namur20, Wageningen University and Research Centre21, King Abdulaziz University22, University of Grenoble23
TL;DR: By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance.
Abstract: Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.
TL;DR: Combined data on LS, spleen diameter, and platelet count can be used to identify patients with compensated cirrhosis most likely to have CSPH and EV.