Showing papers by "University of Turin published in 2015"
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TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
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Paracelsus Private Medical University of Salzburg1, University of Duisburg-Essen2, Semmelweis University3, University of Turin4, Institut Gustave Roussy5, Brown University6, Pontifical Catholic University of Chile7, University of Barcelona8, Trinity College, Dublin9, Istituto Superiore di Sanità10, Ikerbasque11, Pohang University of Science and Technology12, University of Louisville13, Ghent University Hospital14, La Trobe University15, Harvard University16, National University of Singapore17, Maastricht University18, University of Mainz19, University of Cambridge20, Utrecht University21, Agency for Science, Technology and Research22, University of Gothenburg23, University of Valencia24, University of Freiburg25, Aalborg University26, National Research Council27, Paul Ehrlich Institute28, German Red Cross29, University of Oxford30, Karolinska Institutet31
TL;DR: In this paper, the authors summarize recent developments and the current knowledge of extracellular vesicles (EVs) and discuss safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application.
Abstract: Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
954 citations
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TL;DR: The results provide a mechanistic framework for designing highly efficient adsorbents for removing CO2 from various gas mixtures, and yield insights into the conservation of Mg2+ within the ribulose-1,5-bisphosphate carboxylase/oxygenase family of enzymes.
Abstract: The process of carbon capture and sequestration has been proposed as a method of mitigating the build-up of greenhouse gases in the atmosphere. If implemented, the cost of electricity generated by a fossil fuel-burning power plant would rise substantially, owing to the expense of removing CO2 from the effluent stream. There is therefore an urgent need for more efficient gas separation technologies, such as those potentially offered by advanced solid adsorbents. Here we show that diamine-appended metal-organic frameworks can behave as 'phase-change' adsorbents, with unusual step-shaped CO2 adsorption isotherms that shift markedly with temperature. Results from spectroscopic, diffraction and computational studies show that the origin of the sharp adsorption step is an unprecedented cooperative process in which, above a metal-dependent threshold pressure, CO2 molecules insert into metal-amine bonds, inducing a reorganization of the amines into well-ordered chains of ammonium carbamate. As a consequence, large CO2 separation capacities can be achieved with small temperature swings, and regeneration energies appreciably lower than achievable with state-of-the-art aqueous amine solutions become feasible. The results provide a mechanistic framework for designing highly efficient adsorbents for removing CO2 from various gas mixtures, and yield insights into the conservation of Mg(2+) within the ribulose-1,5-bisphosphate carboxylase/oxygenase family of enzymes.
929 citations
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TL;DR: An extensive view on the role of hydroxyl radical in different environmental compartments and in laboratory systems is provided, with the aim of drawing more attention to this emerging issue of great concern.
Abstract: The hydroxyl radical (•OH) is one of the most powerful oxidizing agents, able to react unselectively and instantaneously with the surrounding chemicals, including organic pollutants and inhibitors. The •OH radicals are omnipresent in the environment (natural waters, atmosphere, interstellar space, etc.), including biological systems where •OH has an important role in immunity metabolism. We provide an extensive view on the role of hydroxyl radical in different environmental compartments and in laboratory systems, with the aim of drawing more attention to this emerging issue. Further research on processes related to the hydroxyl radical chemistry in the environmental compartments is highly demanded. A comprehensive understanding of the sources and sinks of •OH radicals including their implications in the natural waters and in the atmosphere is of crucial importance, including the way irradiated chromophoric dissolved organic matter in surface waters yields •OH through the H2O2-independent pathway, and the ...
892 citations
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TL;DR: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma, and no maximum tolerated dose was identified in part 1.
Abstract: BACKGROUND Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1–2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. RESULTS No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytope nia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288.)
882 citations
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TL;DR: The results indicate that the CRC genome adapts dynamically to intermittent drug schedules and provide a molecular explanation for the efficacy of rechallenge therapies based on EGFR blockade.
Abstract: By monitoring ctDNA, the authors reveal the dynamic adaption of clonal populations in colorectal cancer patients treated with anti-EGFR therapy, suggesting that therapeutic re-challenge may have some benefit.
863 citations
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Institut national de la recherche agronomique1, University of Lorraine2, United States Department of Energy3, Clark University4, Hungarian Academy of Sciences5, Helmholtz Centre for Environmental Research - UFZ6, Lund University7, University of Hasselt8, Universidade Federal de Viçosa9, University of Lyon10, University of Turin11, King Abdulaziz University12, Aix-Marseille University13, University of Oslo14, Swedish University of Agricultural Sciences15, Max Planck Society16, University of Bremen17, Harvard University18, Swiss Federal Institute for Forest, Snow and Landscape Research19, Pierre-and-Marie-Curie University20, University of Cologne21
TL;DR: Convergent evolution of the mycorrhizal habit in fungi occurred via the repeated evolution of a 'symbiosis toolkit', with reduced numbers of PCWDEs and lineage-specific suites of myCorrhiza-induced genes.
Abstract: To elucidate the genetic bases of mycorrhizal lifestyle evolution, we sequenced new fungal genomes, including 13 ectomycorrhizal (ECM), orchid (ORM) and ericoid (ERM) species, and five saprotrophs, which we analyzed along with other fungal genomes. Ectomycorrhizal fungi have a reduced complement of genes encoding plant cell wall-degrading enzymes (PCWDEs), as compared to their ancestral wood decayers. Nevertheless, they have retained a unique array of PCWDEs, thus suggesting that they possess diverse abilities to decompose lignocellulose. Similar functional categories of nonorthologous genes are induced in symbiosis. Of induced genes, 7-38% are orphan genes, including genes that encode secreted effector-like proteins. Convergent evolution of the mycorrhizal habit in fungi occurred via the repeated evolution of a 'symbiosis toolkit', with reduced numbers of PCWDEs and lineage-specific suites of mycorrhiza-induced genes.
799 citations
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TL;DR: In this article, the authors provide an updated recommendation for the usage of sets of parton distribution functions (PDFs) and the assessment of PDF and PDF+$\alpha_s$ uncertainties suitable for applications at the LHC Run II.
Abstract: We provide an updated recommendation for the usage of sets of parton distribution functions (PDFs) and the assessment of PDF and PDF+$\alpha_s$ uncertainties suitable for applications at the LHC Run II. We review developments since the previous PDF4LHC recommendation, and discuss and compare the new generation of PDFs, which include substantial information from experimental data from the Run I of the LHC. We then propose a new prescription for the combination of a suitable subset of the available PDF sets, which is presented in terms of a single combined PDF set. We finally discuss tools which allow for the delivery of this combined set in terms of optimized sets of Hessian eigenvectors or Monte Carlo replicas, and their usage, and provide some examples of their application to LHC phenomenology.
683 citations
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TL;DR: The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV.
Abstract: The gamma-ray sky can be decomposed into individually detected sources, diffuse emission attributed to the interactions of Galactic cosmic rays with gas and radiation fields, and a residual all-sky emission component commonly called the isotropic diffuse gamma-ray background (IGRB). The IGRB comprises all extragalactic emissions too faint or too diffuse to be resolved in a given survey, as well as any residual Galactic foregrounds that are approximately isotropic. The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV. Improvements in event selection and characterization of cosmic-ray backgrounds, better understanding of the diffuse Galactic emission, and a longer data accumulation of 50 months, allow for a refinement and extension of the IGRB measurement with the LAT, now covering the energy range from 100 MeV to 820 GeV. The IGRB spectrum shows a significant high-energy cutoff feature, and can be well described over nearly four decades in energy by a power law with exponential cutoff having a spectral index of 2.32 plus or minus 0.02 and a break energy of (279 plus or minus 52) GeV using our baseline diffuse Galactic emission model. The total intensity attributed to the IGRB is (7.2 plus or minus 0.6) x 10(exp -6) cm(exp -2) s(exp -1) sr(exp -1) above 100 MeV, with an additional +15%/-30% systematic uncertainty due to the Galactic diffuse foregrounds.
680 citations
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TL;DR: The third catalog of active galactic nuclei (AGNs) detected by the Fermi-LAT (3LAC) is presented in this paper, which is based on the 3FGL of sources detected between 100 MeV and 300 GeV.
Abstract: The third catalog of active galactic nuclei (AGNs) detected by the Fermi-LAT (3LAC) is presented. It is based on the third Fermi-LAT catalog (3FGL) of sources detected between 100 MeV and 300 GeV w ...
668 citations
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Wellcome Trust Sanger Institute1, University of Oxford2, Genentech3, Vita-Salute San Raffaele University4, University of Turin5, European Bioinformatics Institute6, University of Paris-Sud7, King Abdulaziz University8, Western General Hospital9, Institut national de la recherche agronomique10, University of Leicester11, International Potato Center12, Joint Genome Institute13, Queen Mary University of London14, French Institute for Research in Computer Science and Automation15, University of Trento16, University of Chile17, Pfizer18, Pompeu Fabra University19, Catalan Institution for Research and Advanced Studies20, Seoul National University21, Ontario Institute for Cancer Research22, University of California, Los Angeles23, Iowa State University24, Peking University25, University of Cambridge26, Karolinska Institutet27, University of Rennes28, Cold Spring Harbor Laboratory29
TL;DR: The latest version of the BioMart Community Portal comes with many new databases that have been created by the ever-growing community and comes with better support and extensibility for data analysis and visualization tools.
Abstract: The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.
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TL;DR: In this paper, the branching fraction ratio R(D)(()*()) of (B) over bar → D-(*())tau(-)(nu)over bar (tau) relative to (B), where l = e or mu, was measured using the full Belle data sample.
Abstract: We report a measurement of the branching fraction ratios R(D)(()*()) of (B) over bar -> D-(*())tau(-)(nu) over bar (tau) relative to (B) over bar -> D-(*())l(-)(nu) over barl (where l = e or mu) using the full Belle data sample of 772 x 10(6)B (B) over bar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The measured values are R(D) = 0.375 +/- 0.064(stat) +/- 0.026(syst) and R(D*) = 0.293 +/- 0.038 (stat) +/- 0.015 (syst). The analysis uses hadronic reconstruction of the tag-side B meson and purely leptonic t decays. The results are consistent with earlier measurements and do not show a significant deviation from the standard model prediction.
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Harvard University1, Niigata University2, University of California, San Francisco3, Duke University4, University of Bonn5, Heidelberg University6, University of Texas MD Anderson Cancer Center7, University of Colorado Denver8, Queen's University9, University of Groningen10, Henry Ford Health System11, University of California, Irvine12, University of Western Ontario13, Stanford University14, University of Maryland, Baltimore15, University of Virginia16, University of Turin17, Cleveland Clinic18, Erasmus University Rotterdam19
TL;DR: Recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials are presented and hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity.
Abstract: CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.
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21 Oct 2015-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: The Pierre Auger Observatory as mentioned in this paper, the world's largest cosmic ray observatory, has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr.
Abstract: The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world's largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and characteristics of cosmic rays above $10^{17}$ eV and to study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water-Cherenkov particle detector stations spread over 3000 km$^2$ overlooked by 24 air fluorescence telescopes. In addition, three high elevation fluorescence telescopes overlook a 23.5 km$^2$, 61 detector infill array. The Observatory has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Auger Observatory.
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TL;DR: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy and addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH).
Abstract: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations
MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 – 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 – 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early ( MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).
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Stanford University1, University of Turin2, Université libre de Bruxelles3, University of Cambridge4, Austrian Academy of Sciences5, Genentech6, Harvard University7, German Cancer Research Center8, Cornell University9, University of Texas MD Anderson Cancer Center10, Columbia University11, Memorial Sloan Kettering Cancer Center12, National Institutes of Health13, Research Institute of Molecular Pathology14, French Institute of Health and Medical Research15
TL;DR: A meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity and devised potential solutions are presented here.
Abstract: The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here.
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TL;DR: It is shown that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes and decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.
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Washington University in St. Louis1, The Chinese University of Hong Kong2, Boston Children's Hospital3, Newcastle University4, National Scientific and Technical Research Council5, University of California, San Francisco6, University of Turin7, University of California, San Diego8, Saint Louis University9, Northwestern University10
TL;DR: No effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery, however, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring.
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University of Turin1, University of Salamanca2, Mayo Clinic3, Roswell Park Cancer Institute4, Emory University5, VU University Medical Center6, National and Kapodistrian University of Athens7, Cross Cancer Institute8, University of Ostrava9, Harvard University10, Cedars-Sinai Medical Center11, University of Navarra12, Erasmus University Rotterdam13
TL;DR: The frailty score predicts mortality and the risk of toxicity in elderly myeloma patients and is proposed for the measurement of frailty in designing future clinical trials.
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TL;DR: Analysis of CRC expression data from patient-derived xenografts shows that the distinctive transcriptional and clinical features of the SSM subtype can be ascribed to its particularly abundant stromal component.
Abstract: Recent studies identified a poor-prognosis stem/serrated/mesenchymal (SSM) transcriptional subtype of colorectal cancer (CRC). We noted that genes upregulated in this subtype are also prominently expressed by stromal cells, suggesting that SSM transcripts could derive from stromal rather than epithelial cancer cells. To test this hypothesis, we analyzed CRC expression data from patient-derived xenografts, where mouse stroma supports human cancer cells. Species-specific expression analysis showed that the mRNA levels of SSM genes were mostly due to stromal expression. Transcriptional signatures built to specifically report the abundance of cancer-associated fibroblasts (CAFs), leukocytes or endothelial cells all had significantly higher expression in human CRC samples of the SSM subtype. High expression of the CAF signature was associated with poor prognosis in untreated CRC, and joint high expression of the stromal signatures predicted resistance to radiotherapy in rectal cancer. These data show that the distinctive transcriptional and clinical features of the SSM subtype can be ascribed to its particularly abundant stromal component.
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TL;DR: The present review discusses the potential of locusts, grasshoppers, termites, yellow mealworms, Asiatic rhinoceros beetles, superworms, domesticated silkworms, common houseflies, common mosquitoes and black soldier flies for use as fishmeal and/or fish oil replacement in the fish diet.
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TL;DR: A combination of all inclusive deep inelastic cross sections previously published by the H1 and ZEUS collaborations at HERA for neutral and charged current scattering for zero beam polarisation is presented in this paper.
Abstract: A combination is presented of all inclusive deep inelastic cross sections previously published by the H1 and ZEUS collaborations at HERA for neutral and charged current $e^{\pm}p$ scattering for zero beam polarisation. The data were taken at proton beam energies of 920, 820, 575 and 460 GeV and an electron beam energy of 27.5 GeV. The data correspond to an integrated luminosity of about 1 fb$^{-1}$ and span six orders of magnitude in negative four-momentum-transfer squared, $Q^2$, and Bjorken $x$. The correlations of the systematic uncertainties were evaluated and taken into account for the combination. The combined cross sections were input to QCD analyses at leading order, next-to-leading order and at next-to-next-to-leading order, providing a new set of parton distribution functions, called HERAPDF2.0. In addition to the experimental uncertainties, model and parameterisation uncertainties were assessed for these parton distribution functions. Variants of HERAPDF2.0 with an alternative gluon parameterisation, HERAPDF2.0AG, and using fixed-flavour-number schemes, HERAPDF2.0FF, are presented. The analysis was extended by including HERA data on charm and jet production, resulting in the variant HERAPDF2.0Jets. The inclusion of jet-production cross sections made a simultaneous determination of these parton distributions and the strong coupling constant possible, resulting in $\alpha_s(M_Z)=0.1183 \pm 0.0009 {\rm(exp)} \pm 0.0005{\rm (model/parameterisation)} \pm 0.0012{\rm (hadronisation)} ^{+0.0037}_{-0.0030}{\rm (scale)}$. An extraction of $xF_3^{\gamma Z}$ and results on electroweak unification and scaling violations are also presented.
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Royal Free Hospital1, Institut Gustave Roussy2, University of Perugia3, University of Turin4, Imperial College London5, University of Milan6, University of Bern7, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico8, Memorial Sloan Kettering Cancer Center9, University of Marburg10, Autonomous University of Barcelona11, Erasmus University Rotterdam12, Uppsala University13, University of Genoa14, Churchill Hospital15, Kyushu University16, National Institutes of Health17, National and Kapodistrian University of Athens18, University of Reims Champagne-Ardenne19, University of Copenhagen20, Medical University of Silesia21, Curie Institute22, Aberdeen Royal Infirmary23, University College Dublin24, Charité25, Charles University in Prague26, University College London27, University of Freiburg28, Peking Union Medical College29
TL;DR: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up, and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC.
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Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam2 +2802 more•Institutions (215)
TL;DR: In this paper, the branching fractions of the B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) were observed.
Abstract: The standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) are especially interesting because of their sensitivity to theories that extend the standard model. The standard model predicts that the B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) decays are very rare, with about four of the former occurring for every billion B-s(0) mesons produced, and one of the latter occurring for every ten billion B-0 mesons(1). A difference in the observed branching fractions with respect to the predictions of the standard model would provide a direction in which the standard model should be extended. Before the Large Hadron Collider (LHC) at CERN2 started operating, no evidence for either decay mode had been found. Upper limits on the branching fractions were an order of magnitude above the standard model predictions. The CMS (Compact Muon Solenoid) and LHCb(Large Hadron Collider beauty) collaborations have performed a joint analysis of the data from proton-proton collisions that they collected in 2011 at a centre-of-mass energy of seven teraelectronvolts and in 2012 at eight teraelectronvolts. Here we report the first observation of the B-s(0)->mu(+)mu(-) decay, with a statistical significance exceeding six standard deviations, and the best measurement so far of its branching fraction. Furthermore, we obtained evidence for the B-0 ->mu(+)mu(-) decay with a statistical significance of three standard deviations. Both measurements are statistically compatible with standard model predictions and allow stringent constraints to be placed on theories beyond the standard model. The LHC experiments will resume taking data in 2015, recording proton-proton collisions at a centre-of-mass energy of 13 teraelectronvolts, which will approximately double the production rates of B-s(0) and B-0 mesons and lead to further improvements in the precision of these crucial tests of the standard model.
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Mae Fah Luang University1, World Agroforestry Centre2, King Saud University3, Guizhou University4, Goa University5, Centre national de la recherche scientifique6, Chinese Academy of Sciences7, Beijing Forestry University8, Botanic Garden Meise9, Indonesian Institute of Sciences10, University of Mauritius11, Thailand National Science and Technology Development Agency12, Landcare Research13, University of Toronto14, Iranian Research Organization for Science and Technology15, University of Gothenburg16, National Taiwan Ocean University17, Universidade Federal de Viçosa18, Universidade Nova de Lisboa19, Lincoln Memorial University20, Facultad de Ciencias Exactas y Naturales21, Ahi Evran University22, University of Arkansas23, Royal Botanic Garden Edinburgh24, University of British Columbia25, University of Turin26, Sohag University27, Flinders University28, Chiang Mai University29
TL;DR: The present paper introduces the FoF database to the scientific community and briefly reviews some of the problems associated with classification and identification of the main fungal groups.
Abstract: Taxonomic names are key links between various databases that store information on different organisms. Several global fungal nomenclural and taxonomic databases (notably Index Fungorum, Species Fungorum and MycoBank) can be sourced to find taxonomic details about fungi, while DNA sequence data can be sourced from NCBI, EBI and UNITE databases. Although the sequence data may be linked to a name, the quality of the metadata is variable and generally there is no corresponding link to images, descriptions or herbarium material. There is generally no way to establish the accuracy of the names in these genomic databases, other than whether the submission is from a reputable source. To tackle this problem, a new database (FacesofFungi), accessible at www.facesoffungi.org
(FoF) has been established. This fungal database allows deposition of taxonomic data, phenotypic details and other useful data, which will enhance our current taxonomic understanding and ultimately enable mycologists to gain better and updated insights into the current fungal classification system. In addition, the database will also allow access to comprehensive metadata including descriptions of voucher and type specimens. This database is user-friendly, providing links and easy access between taxonomic ranks, with the classification system based primarily on molecular data (from the literature and via updated web-based phylogenetic trees), and to a lesser extent on morphological data when molecular data are unavailable. In FoF species are not only linked to the closest phylogenetic representatives, but also relevant data is provided, wherever available, on various applied aspects, such as ecological, industrial, quarantine and chemical uses. The data include the three main fungal groups (Ascomycota, Basidiomycota, Basal fungi) and fungus-like organisms. The FoF webpage is an output funded by the Mushroom Research Foundation which is an NGO with seven directors with mycological expertise. The webpage has 76 curators, and with the help of these specialists, FoF will provide an updated natural classification of the fungi, with illustrated accounts of species linked to molecular data. The present paper introduces the FoF database to the scientific community and briefly reviews some of the problems associated with classification and identification of the main fungal groups. The structure and use of the database is then explained. We would like to invite all mycologists to contribute to these web pages.
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TL;DR: KPC-Kp infections are associated with high mortality and treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.
Abstract: Objectives Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals. Methods The cohort included 661 adults with bloodstream infections (BSIs; n = 447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. Results Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤8 mg/L. Conclusions KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.
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University of Warsaw1, Yerevan Physics Institute2, Argonne National Laboratory3, RWTH Aachen University4, Karlsruhe Institute of Technology5, City University of New York6, New York City College of Technology7, University of Turin8, University of Bern9, CERN10, University of Oxford11, Folkwang University of the Arts12, Florida State University13
TL;DR: An update of standard model predictions for the inclusive branching ratios of the B mesons is presented, incorporating all results for the O(α_{s}^{2}) and lower-order perturbative corrections that have been calculated after 2006.
Abstract: Weak radiative decays of the B mesons belong to the most important flavor changing processes that provide constraints on physics at the TeV scale. In the derivation of such constraints, accurate standard model predictions for the inclusive branching ratios play a crucial role. In the current Letter we present an update of these predictions, incorporating all our results for the O(α2s) and lower-order perturbative corrections that have been calculated after 2006. New estimates of nonperturbative effects are taken into account, too. For the CP- and isospin-averaged branching ratios, we find Bsγ=(3.36±0.23)×10−4 and Bdγ=(1.73+0.12−0.22)×10−5, for Eγ>1.6 GeV. Both results remain in agreement with the current experimental averages. Normalizing their sum to the inclusive semileptonic branching ratio, we obtain Rγ≡(Bsγ+Bdγ)/Bclν=(3.31±0.22)×10−3. A new bound from Bsγ on the charged Higgs boson mass in the two-Higgs-doublet-model II reads MH±>480 GeV at 95% C.L.
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TL;DR: An overview of skeletal muscle intracellular pathways determining fiber size is given, and the evidences supporting the role of inflammation in impairing muscle homeostasis and myogenesis, potentially determining muscle atrophy are discussed.
Abstract: Skeletal muscle mass is subject to rapid changes according to growth stimuli inducing both hypertrophy, through increased protein synthesis, and hyperplasia, activating the myogenic program. Muscle wasting, characteristic of several pathological states associated with local or systemic inflammation, has been for long considered to rely on the alteration of myofiber intracellular pathways regulated by both hormones and cytokines, eventually leading to impaired anabolism and increased protein breakdown. However, there are increasing evidences that even alterations of the myogenic/regenerative program play a role in the onset of muscle wasting, even though the precise mechanisms involved are far from being fully elucidated. The comprehension of the links potentially occurring between impaired myogenesis and increased catabolism would allow the definition of effective strategies aimed at counteracting muscle wasting. The first part of this review gives an overview of skeletal muscle intracellular pathways determining fiber size, while the second part considers the cells and the regulatory pathways involved in the myogenic program. In both parts are discussed the evidences supporting the role of inflammation in impairing muscle homeostasis and myogenesis, potentially determining muscle atrophy.
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Vardan Khachatryan, Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1 +2114 more•Institutions (146)
TL;DR: In this article, the spin-parity and tensor structure of the interactions of the recently discovered Higgs boson is performed using the H to ZZ, Z gamma*, gamma* gamma* to 4 l, H to WW to l nu l nu, and H to gamma gamma decay modes.
Abstract: The study of the spin-parity and tensor structure of the interactions of the recently discovered Higgs boson is performed using the H to ZZ, Z gamma*, gamma* gamma* to 4 l, H to WW to l nu l nu, and H to gamma gamma decay modes. The full dataset recorded by the CMS experiment during the LHC Run 1 is used, corresponding to an integrated luminosity of up to 5.1 inverse femtobarns at a center-of-mass energy of 7 TeV and up to 19.7 inverse femtobarns at 8 TeV. A wide range of spin-two models is excluded at a 99% confidence level or higher, or at a 99.87% confidence level for the minimal gravity-like couplings, regardless of whether assumptions are made on the production mechanism. Any mixed-parity spin-one state is excluded in the ZZ and WW modes at a greater than 99.999% confidence level. Under the hypothesis that the resonance is a spin-zero boson, the tensor structure of the interactions of the Higgs boson with two vector bosons ZZ, Z gamma, gamma gamma, and WW is investigated and limits on eleven anomalous contributions are set. Tighter constraints on anomalous HVV interactions are obtained by combining the HZZ and HWW measurements. All observations are consistent with the expectations for the standard model Higgs boson with the quantum numbers J[PC]=0[++].
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Academic Center for Dentistry Amsterdam1, University of Kiel2, Complutense University of Madrid3, National and Kapodistrian University of Athens4, University College London5, University of Louisville6, Yeditepe University7, University of Marburg8, The Catholic University of America9, University of Turin10, University of Pisa11
TL;DR: Data support the belief that professionally administered plaque control significantly improves gingival inflammation and lowers plaque scores, with some evidence that reinforcement of oral hygiene provides further benefit.
Abstract: Periodontitis is a ubiquitous and irreversible inflammatory condition and represents a significant public health burden. Severe periodontitis affects over 11% of adults, is a major cause of tooth loss impacting negatively upon speech, nutrition, quality of life and self-esteem, and has systemic inflammatory consequences. Periodontitis is preventable and treatment leads to reduced rates of tooth loss and improved quality of life. However, successful treatment necessitates behaviour change in patients to address lifestyle risk factors (e.g. smoking) and, most importantly, to attain and sustain high standards of daily plaque removal, lifelong. While mechanical plaque removal remains the bedrock of successful periodontal disease management, in high-risk patients it appears that the critical threshold for plaque accumulation to trigger periodontitis is low, and such patients may benefit from adjunctive agents for primary prevention of periodontitis. Aim The aims of this working group were to systematically review the evidence for primary prevention of periodontitis by preventing gingivitis via four approaches: 1) the efficacy of mechanical self-administered plaque control regimes; 2) the efficacy of self-administered inter-dental mechanical plaque control; 3) the efficacy of adjunctive chemical plaque control; and 4) anti-inflammatory (sole or adjunctive) approaches. Methods Two meta-reviews (mechanical plaque removal) and two traditional systematic reviews (chemical plaque control/anti-inflammatory agents) formed the basis of this consensus. Results Data support the belief that professionally administered plaque control significantly improves gingival inflammation and lowers plaque scores, with some evidence that reinforcement of oral hygiene provides further benefit. Re-chargeable power toothbrushes provide small but statistically significant additional reductions in gingival inflammation and plaque levels. Flossing cannot be recommended other than for sites of gingival and periodontal health, where inter-dental brushes (IDBs) will not pass through the interproximal area without trauma. Otherwise, IDBs are the device of choice for interproximal plaque removal. Use of local or systemic anti-inflammatory agents in the management of gingivitis has no robust evidence base. We support the almost universal recommendations that all people should brush their teeth twice a day for at least 2 min. with fluoridated dentifrice. Expert opinion is that for periodontitis patients 2 min. is likely to be insufficient, especially when considering the need for additional use of inter-dental cleaning devices. In patients with gingivitis once daily inter-dental cleaning is recommended and the adjunctive use of chemical plaque control agents offers advantages in this group.